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Blanco R, Muñoz JP. Human Cytomegalovirus Infection and Breast Cancer: A Literature Review of Clinical and Experimental Data. BIOLOGY 2025; 14:174. [PMID: 40001942 PMCID: PMC11851556 DOI: 10.3390/biology14020174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/05/2024] [Accepted: 12/09/2024] [Indexed: 02/27/2025]
Abstract
Breast cancer (BC) remains a significant global health challenge, highlighting the need for continued research into novel risk factors, diagnostic approaches, and personalized treatments. Among emerging risk factors, viral infections have been implicated as potential contributors to breast carcinogenesis and BC progression. Recent evidence suggests that specific oncogenic strains of human cytomegalovirus (HCMV) may have the capacity to transform human mammary epithelial cells. This review assesses clinical data regarding HCMV presence in both tumor and non-tumor breast tissues, examining the role of HCMV oncoproteins in BC development and progression. Current findings indicate a higher prevalence of HCMV infection in breast carcinomas compared to non-tumor tissues, associated with an elevated risk of BC. Additionally, the HCMV-driven breast carcinogenesis model proposed here suggests that HCMV oncoproteins may activate multiple oncogenic pathways, fostering cell proliferation, survival, and tumor development. A deeper understanding of the role of HCMV in BC could enhance risk stratification and support the creation of targeted therapeutic strategies.
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Affiliation(s)
| | - Juan P. Muñoz
- Laboratorio de Bioquímica, Departamento de Química, Facultad de Ciencias, Universidad de Tarapacá, Arica 1000007, Chile
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Spencer JV, Liu J, Deyarmin B, Hu H, Shriver CD, Somiari S. Cytokine levels in breast cancer are highly dependent on cytomegalovirus (CMV) status. Breast Cancer Res Treat 2024; 208:631-641. [PMID: 39172306 PMCID: PMC11522175 DOI: 10.1007/s10549-024-07459-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 08/07/2024] [Indexed: 08/23/2024]
Abstract
PURPOSE Breast cancer accounts for 30% of all female cancers in the US. Cytomegalovirus (CMV), a herpesvirus that establishes lifelong infection, may play a role in breast cancer. CMV is not oncogenic, yet viral DNA and proteins have been detected in breast tumors, indicating possible contribution to tumor development. CMV encodes cmvIL-10, a homolog of human cellular IL-10 (cIL-10) with potent immunosuppressive activities. We investigated the relationship between CMV infection, cytokines, and breast cancer. METHODS We evaluated CMV serostatus and cytokine levels in plasma of women with benign breast disease (n = 38), in situ carcinoma (n = 41), invasive carcinoma, no lymph node involvement (Inv/LN-; n = 41), and invasive with lymph node involvement (Inv/LN+; n = 37). RESULTS Fifty percent of the patient samples (n = 79) were CMV seropositive. There was no correlation between CMV status and diagnosis (p = 0.75). For CMV+ patients, there was a trend toward higher CMV IgG levels in invasive disease (p = 0.172). CmvIL-10 levels were higher in CMV+ in situ patients compared to the Inv/LN- and Inv/LN+ groups (p = 0.020). Similarly, cIL-10 levels were higher in CMV+ in situ patients compared to the Inv/LN- and Inv/LN+ groups (p = 0.043). The results were quite different in CMV- patients where cIL-10 levels were highest in Inv/LN- compared to benign, in situ, or Inv/LN+ (p = 0.019). African American patients were significantly associated with CMV+ status (p = 0.001) and had lower cmvIL-10 levels than Caucasian patients (p = 0.046). CONCLUSION No association was observed between CMV IgG and diagnosis, but CMV infection influences cytokine production and contributes to altered cytokine profiles in breast cancer.
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Affiliation(s)
- Juliet V Spencer
- Department of Biology, Texas Woman's University, Denton, TX, USA.
| | - Jianfang Liu
- Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA
| | - Brenda Deyarmin
- Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA
| | - Hai Hu
- Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA
| | - Craig D Shriver
- Murtha Cancer Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Stella Somiari
- Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA
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Fathy A, Abdelrazek MA, Attallah AM, Abouzid A, El-Far M. Hepatitis C virus may accelerate breast cancer progression by increasing mutant p53 and c-Myc oncoproteins circulating levels. Breast Cancer 2024; 31:116-123. [PMID: 37973687 PMCID: PMC10764473 DOI: 10.1007/s12282-023-01519-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 10/19/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) was reported to relate to polymorphous and frequent extrahepatic manifestation. Despite the limited studies, HCV viral oncoproteins may be implicated in breast cancer (BC) tumor aggressiveness. In a trial to elucidate a mechanistic link, this study aimed to investigate a mutant p53 and c-Myc oncoprotein expression levels in BC patients with and without HCV infection. METHODS A total of 215 BC patients (119 infected and 96 non-infected with HCV) were collected. ELISA was used for detection of anti-HCV antibodies, mutant p53, c-Myc, HCV-NS4, CEA, CA 125, and CA-15.3. RESULTS HCV infection was related to BC late stages, lymph-node invasion, distant metastasis, high grades, and large size. HCV-infected patients had a significantly (P < 0.05) higher WBCs, ALT and AST activity, bilirubin CEA, CA125 and CA15.3 levels, and reduced hemoglobin, albumin, and RBCs count. Regardless of tumor severity, HCV infection was associated with significant elevated levels of mutant p53 (22.5 ± 3.5 µg/mL; 1.9-fold increase) and c-Myc (21.4 ± 1.8 µg/mL; 1.5-fold increase). Among HCV-infected patients, elevated levels of p53 and c-Myc were significantly correlated with elevated tumor markers (CEA, CA 125, and CA15.3) and HCV-NS4 levels. CONCLUSIONS This study concluded that HCV infection may be accompanied with BC severity behavior and this may be owing to elevated expression of mutant p53 and c-Myc oncoproteins.
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Affiliation(s)
- Amira Fathy
- Research and Development Department, Biotechnology Research Center, New Damietta, Egypt
| | - Mohamed A Abdelrazek
- Research and Development Department, Biotechnology Research Center, New Damietta, Egypt.
| | | | - Amr Abouzid
- Surgical Oncology Department, Mansoura Oncology Centre, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mohamed El-Far
- Biochemistry Division, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt.
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Larios-Serrato V, Martínez-Ezquerro JD, Valdez-Salazar HA, Torres J, Camorlinga-Ponce M, Piña-Sánchez P, Ruiz-Tachiquín ME. Copy number alterations and epithelial‑mesenchymal transition genes in diffuse and intestinal gastric cancers in Mexican patients. Mol Med Rep 2022; 25:191. [PMID: 35362543 PMCID: PMC8985205 DOI: 10.3892/mmr.2022.12707] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 02/28/2022] [Indexed: 01/06/2023] Open
Abstract
Gastric cancer (GC) is a common malignancy with the highest mortality rate among diseases of the digestive system, worldwide. The present study of GC alterations is crucial to the understanding of tumor biology and the establishment of important aspects of cancer prognosis and treatment response. In the present study, DNA from Mexican patients with diffuse GC (DGC), intestinal GC (IGC) or non‑atrophic gastritis (NAG; control) was purified and whole‑genome analysis was performed with high‑density arrays. Shared and unique copy number alterations (CNA) were identified between the different tissues involving key genes and signaling pathways associated with cancer. This led to the molecular distinction and identification of the most relevant molecular functions to be identified. A more detailed bioinformatics analysis of epithelial‑mesenchymal transition (EMT) genes revealed that the altered network associated with chromosomal alterations included 11 genes that were shared between DGC, IGC and NAG, as well as 19 DGC‑ and 7 IGC‑exclusive genes. Furthermore, the main molecular functions included adhesion, angiogenesis, migration, metastasis, morphogenesis, proliferation and survival. The present study provided the first whole‑genome high‑density array analysis in Mexican patients with GC and revealed shared and exclusive CNA‑associated genes in DGC and IGC. In addition, a bioinformatics‑predicted network was generated, focusing on CNA‑altered genes associated with EMT and the hallmarks of cancer, as well as precancerous alterations that may lead to GC. Molecular signatures of diffuse and intestinal GC, predicted bioinformatically, involve common and distinct CNA‑EMT genes related to the hallmarks of cancer that are potential candidates for screening biomarkers of GC, including early stages.
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Affiliation(s)
- Violeta Larios-Serrato
- Laboratory of Biotechnology and Genomic Bioinformatics, National School of Biological Sciences (ENCB), National Polytechnic Institute (IPN), Lázaro Cárdenas Professional Unit, Mexico City 11340, Mexico
| | - José-Darío Martínez-Ezquerro
- Epidemiological and Health Services Research Unit, Aging Area (UIESSAE), XXI Century National Medical Center, Mexican Social Security Institute (IMSS), Mexico City 06720, Mexico
| | - Hilda-Alicia Valdez-Salazar
- Infectious and Parasitic Diseases Medical Research Unit (UIMEIP), High Specialty Medical Unit (UMAE)‑Pediatrics Hospital 'Dr. Silvestre Frenk Freund', XXI Century National Medical Center, IMSS, Mexico City 06720, Mexico
| | - Javier Torres
- Infectious and Parasitic Diseases Medical Research Unit (UIMEIP), High Specialty Medical Unit (UMAE)‑Pediatrics Hospital 'Dr. Silvestre Frenk Freund', XXI Century National Medical Center, IMSS, Mexico City 06720, Mexico
| | - Margarita Camorlinga-Ponce
- Infectious and Parasitic Diseases Medical Research Unit (UIMEIP), High Specialty Medical Unit (UMAE)‑Pediatrics Hospital 'Dr. Silvestre Frenk Freund', XXI Century National Medical Center, IMSS, Mexico City 06720, Mexico
| | - Patricia Piña-Sánchez
- Oncological Diseases Medical Research Unit (UIMEO), UMAE‑Oncology Hospital, XXI Century National Medical Center, Mexican Social Security Institute (IMSS), Mexico City 06720, Mexico
| | - Martha-Eugenia Ruiz-Tachiquín
- Oncological Diseases Medical Research Unit (UIMEO), UMAE‑Oncology Hospital, XXI Century National Medical Center, Mexican Social Security Institute (IMSS), Mexico City 06720, Mexico
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Human Cytomegalovirus Seropositivity and Viral DNA in Breast Tumors Are Associated with Poor Patient Prognosis. Cancers (Basel) 2022; 14:cancers14051148. [PMID: 35267456 PMCID: PMC8909033 DOI: 10.3390/cancers14051148] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 02/18/2022] [Accepted: 02/18/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Human cytomegalovirus (HCMV) infects 40–70% of adult populations in developed countries and this is thought to be involved in breast cancer progression; however, reports of detection of the viral genome in breast tumors ranges from 0–100%. We optimized a method that is both sensitive and specific to detect HCMV DNA in tissues from Canadian breast cancer patients. Only ~42% of HCMV-seropositive patients expressed viral DNA in their breast tumors. Viral transcription was not detected in any HCMV-infected breast tumors, indicating a latent infection; however, HCMV seropositivity and the presence of latent infections in breast tumors were independently, and in combination, associated with increased metastasis. HCMV DNA-positive tumors were also associated with lower relapse-free survival. Therefore, HCMV infection status should be accounted for during the monitoring and treatment of breast cancer patients. Prevention or reducing the effects of HCMV infection could decrease morbidity and mortality from metastatic disease. Abstract Human cytomegalovirus (HCMV) infects 40–70% of adults in developed countries. Detection of HCMV DNA and/or proteins in breast tumors varies considerably, ranging from 0–100%. In this study, nested PCR to detect HCMV glycoprotein B (gB) DNA in breast tumors was shown to be sensitive and specific in contrast to the detection of DNA for immediate early genes. HCMV gB DNA was detected in 18.4% of 136 breast tumors while 62.8% of 94 breast cancer patients were seropositive for HCMV. mRNA for the HCMV immediate early gene was not detected in any sample, suggesting viral latency in breast tumors. HCMV seropositivity was positively correlated with age, body mass index and menopause. Patients who were HCMV seropositive or had HCMV DNA in their tumors were 5.61 (CI 1.77–15.67, p = 0.003) or 5.27 (CI 1.09–28.75, p = 0.039) times more likely to develop Stage IV metastatic tumors, respectively. Patients with HCMV DNA in tumors experienced reduced relapse-free survival (p = 0.042). Being both seropositive with HCMV DNA-positive tumors was associated with vascular involvement and metastasis. We conclude that determining the seropositivity for HCMV and detection of HCMV gB DNA in the breast tumors could identify breast cancer patients more likely to develop metastatic cancer and warrant special treatment.
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Molecular Detection of Human Cytomegalovirus in Breast Cancer of Iranian Women Using Real-Time PCR. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2021. [DOI: 10.5812/ijcm.115720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: The role of carcinogenic viruses in developing breast cancer has not yet been identified. Many studies have examined the association between breast cancer and human cytomegalovirus (HCMV), but conflicting results have been reported. Objectives: The aim of this study was to evaluate the levels of IgM & IgG antibodies against HCMV by identifying the viral genome in the breast tissue of women with breast cancer. Methods: A total of 60 patients with breast cancer and 60 healthy individuals (40 cases with fibroadenoma and 20 healthy samples) were selected. Serum levels of IgM & IgG antibodies against HCMV were measured by ELISA, and after DNA extraction from the breast tissue, the presence of the cytomegaloviruses (CMV) genome was assessed by Real-Time PCR. Results: Real-time PCR results showed that 20 samples of breast cancer tissue and 5 samples of fibroadenoma were positive for CMV genome (P = 0.001, OR: 5.50, CI 95%: 1.90 - 15.89). All samples had CMV-IgG antibody in their serum, but their mean serum level was higher in the cancer group (48.27 ± 15.99 U/mL) than the control group (40.11 ± 18.01 U/mL) (P = 0.004). However, CMV-IgM anti-viral antibody was positive in 5 cases with cancer and 3 cases in the control group. The mean serum concentration of this antibody was higher in the cancer group (6.60 ± 6.75 U/mL) than the control group (4.92 ± 3.03 U/mL) (P = 0.099). Conclusions: Increased serum levels of anti-CMV antibodies in patients with cancer, as well as the presence of viral genomes in some cases, indicate the carcinogenesis effect of the virus.
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Ghaffari H, Tavakoli A, Nafissi N, Farahmand M, Ghorbani S, Moochani SS, Hashemi-Bahremani M, Alebouyeh MR, Monavari SH. Human cytomegalovirus and Epstein-Barr virus infections in breast cancer: A molecular study on Iranian women. Breast Dis 2021; 40:227-233. [PMID: 33935050 DOI: 10.3233/bd-201019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND OBJECTIVES The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infections in breast cancer pathology is not well understood. Our study aimed to investigate the association of HCMV and EBV infections with breast cancer and distinguish the types of positive EBV and LMP-1 samples in Iranian patients. METHODS Seventy-two formalin-fixed paraffin-embedded (FFPE) breast cancer tissues were analyzed between December 2014 and April 2016. Samples were analyzed for HCMV and EBV using nested-PCR and conventional PCR assays, respectively. Statistical analysis was performed using SPSS software version 18. RESULTS Overall, HCMV and EBV genomes were detected in 6.9% and 16.7% of FFPE breast cancer tissues, respectively. Clinical factors were not statistically associated with the presence of HCMV and EBV. CONCLUSION In this study, we reported EBV and LMP-1 typing in breast carcinoma cases for the first time in Iran. Our findings indicate that HCMV and EBV infections are not associated with the development of breast cancer.
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Affiliation(s)
- Hadi Ghaffari
- Department of Bacteriology and Virology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Ahmad Tavakoli
- Department of Medical Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Nahid Nafissi
- Department of Surgery, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Farahmand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Saied Ghorbani
- Department of Medical Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Somayeh Sadat Moochani
- Department of Medical Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hashemi-Bahremani
- Department of Pathology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahmoud Reza Alebouyeh
- Department of Anesthesia, Faculty of Medicine, Rasoul Akram Medical Center, Iran University of Medical Sciences, Tehran, Iran
| | - Seyed Hamidreza Monavari
- Department of Medical Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
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8
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Maleki F, Sadigh ZA, Sadeghi F, Muhammadnejad A, Farahmand M, Parvin M, Shirkoohi R. Human cytomegalovirus infection in Iranian glioma patients correlates with aging and tumor aggressiveness. J Med Virol 2020; 92:1266-1276. [PMID: 31944314 DOI: 10.1002/jmv.25673] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 01/08/2020] [Indexed: 12/18/2022]
Abstract
Human cytomegalovirus (HCMV), as a ubiquitous and opportunistic virus, is a matter for consideration in broad-spectrum diseases, specifically in immunocompromised individuals. In recent decades, many studies that have evaluated the role of HCMV in inflammation and malignancies, especially in high-grade gliomas, have reported inconsistent results. Thus, this study was conducted to analyze 97 primary gliomas for human CMV UL83 gene and protein through TaqMan real-time polymerase chain reaction and immunohistochemistry, respectively. The results were positive for the UL83 gene and pp65 protein in 71% and 24% of samples, respectively. The frequency of HCMV was significantly higher in glioblastomas than other glioma grades (P < .01 and P < .05 for the UL83 gene and protein, respectively). In addition, the association between the prevalence of HCMV and aging strengthened the virus reactivation hypothesis in gliomas. In conclusion, a high frequency of HCMV infection was found in gliomas that correlated with tumor aggressiveness and age. This study recommends a thorough investigation to determine HCMV infection in gliomas to improve the existing knowledge of its role in glial tumors, its prognostic value, and possible efficient antiviral target therapy.
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Affiliation(s)
- Faezeh Maleki
- Human Viral Vaccine Department, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Alborz Province, Iran
| | - Zohreh-Azita Sadigh
- Human Viral Vaccine Department, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Alborz Province, Iran
| | - Farzin Sadeghi
- Department of Microbiology, Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Ahad Muhammadnejad
- Department of Molecular Genetics, Cancer Biology Research Center, Cancer Institute of Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Farahmand
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Tehran Province, Iran
| | - Mahmoud Parvin
- Department of Pathology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Tehran Province, Iran
| | - Reza Shirkoohi
- Department of Molecular Genetics, Cancer Biology Research Center, Cancer Institute of Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.,Department of Molecular Genetics, Cancer Research Center, Cancer Institute of Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
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9
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Sepahvand P, Makvandi M, Samarbafzadeh A, Talaei-Zadeh A, Ranjbari N, Nisi N, Azaran A, Jalilian S, Pirmoradi R, Makvandi K, Ahmadi Angali K. Human Cytomegalovirus DNA among Women with Breast Cancer. Asian Pac J Cancer Prev 2019; 20:2275-2279. [PMID: 31450895 PMCID: PMC6852836 DOI: 10.31557/apjcp.2019.20.8.2275] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Indexed: 12/20/2022] Open
Abstract
Section Title Breast cancer is the most common cause of death among women worldwide. Although there are many known risk factors in breast cancer development, infectious diseases have appeared as one of the important key to contribute to carcinogenesis formation. The effects of Human Cytomegalovirus (HCMV) on women with breast cancer has been recently studied and reported. To contribute to this research trend, this study was conducted to evaluate the association between HCMV and the women with breast cancer. Objective: This experiment aimed to evaluate HCMV DNA in women with breast cancer in Ahvaz city, Iran. Materials and Methods: A total of 37 formalin fixed paraffin embedded tissues of the patients with ductal breast carcinoma and 35 paraffin embedded tissues of the patients with fibro adenoma as control group were collected. The deparaffinization of all the samples were carried out and the DNA was extracted. Initially, the PCR test was carried out to detect beta –globulin DNA as an internal control. For those samples positive for beta –globulin DNA, Polymerase Chain reaction (PCR) was used to detect HCMV for the tests and control samples. Results: Among 37 ductal breast carcinoma, 20 (54.04%) cases were proved positive for HCMV DNA by PCR. While among the 35 control group (fibroadenoma), 10 (28.57%) cases were positive for HCMV DNA (P >0.028). The prevalences of HCMV DNA among the age groups 30-39, 40-49 and >50 years were 7 (72.22%), 9 (69.23%), 4 (57.14%), respectively (P=0.066). A high frequency of HCMV DNA was detected in tumor grade III, 13/18 (58.33%) compared with tumor grade II, 7/19 (36.84%) (p=0.044). A high frequency of 16/24 (66.66%) of HCMV DNA was found in invasive ductal breast cancer compared with 4/13 (30.76%) HCMV DNA in situ (P<0.028). Conclusion: A high prevalence of 54.05% HCMV was found among the patients with ductal carcinoma. The percentages of the high prevalence of HCMV among age group (40-49) years, tumors grades, and invasive stage were (69.23%), (58.33%), (66.66%), respectively. Further study of HCMV in the latency phase in patients with ductal carcinoma would be necessary to extend our knowledge.
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Affiliation(s)
- Peyman Sepahvand
- Infectious and Tropical Diseases Research Center Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Manoochehr Makvandi
- Infectious and Tropical Diseases Research Center Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ,Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Alireza Samarbafzadeh
- Infectious and Tropical Diseases Research Center Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ,Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Abdulhasan Talaei-Zadeh
- Department of Surgery, Imam Khoeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Pathology, Imam Khoeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Nastaran Ranjbari
- Department of Pathology, Imam Khoeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Nilofar Nisi
- Infectious and Tropical Diseases Research Center Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ,Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Azarakhsh Azaran
- Infectious and Tropical Diseases Research Center Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ,Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Shahram Jalilian
- Infectious and Tropical Diseases Research Center Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ,Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Roya Pirmoradi
- Infectious and Tropical Diseases Research Center Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ,Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Kimia Makvandi
- School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Kambiz Ahmadi Angali
- Biostatistic Department, School of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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10
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Richardson AK, Walker LC, Cox B, Rollag H, Robinson BA, Morrin H, Pearson JF, Potter JD, Paterson M, Surcel HM, Pukkala E, Currie MJ. Breast cancer and cytomegalovirus. Clin Transl Oncol 2019; 22:585-602. [PMID: 31256361 DOI: 10.1007/s12094-019-02164-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Accepted: 06/14/2019] [Indexed: 12/24/2022]
Abstract
PURPOSE To determine whether cytomegalovirus is causally associated with breast cancer and whether cytomegalovirus should be categorised as an oncogenic virus. METHODS We undertook a review of published epidemiological and laboratory studies, using established causal criteria: Bradford Hill criteria to determine whether cytomegalovirus is associated with breast cancer; and Evans/Mueller criteria to determine whether cytomegalovirus should be categorised as an oncogenic virus. RESULTS Although there are inconsistencies in the findings of published epidemiological and laboratory studies, these may be explained by factors such as: differences in timing of blood samples, differences in selection of cases and controls, or high cytomegalovirus seroprevalence among participants in the epidemiological studies; and, in the laboratory studies, differences in sample preparations, age of sample, whether or not paired breast cancer and normal breast tissue samples were used, differences in the tests, primers and/or antibodies used, differences in histological types of breast cancer studied, and/or features of the virus. CONCLUSIONS Overall, the results of published studies of cytomegalovirus and breast cancer suggest cytomegalovirus is a causal factor for at least some types of breast cancer. If the evidence for a link between cytomegalovirus and breast cancer continues to strengthen, further research could lead to: targeted screening; therapy using antiviral drugs; and, perhaps, primary prevention of a significant proportion of breast cancer. Vaccination against viruses has already been shown to be effective in preventing cervix and liver cancer; cytomegalovirus vaccines are already under development.
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Affiliation(s)
- A K Richardson
- Wayne Francis Cancer Epidemiology Research Group, School of Health Sciences, University of Canterbury, Christchurch, New Zealand.
| | - L C Walker
- Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch, New Zealand
| | - B Cox
- Hugh Adam Cancer Epidemiology Unit, Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand
| | - H Rollag
- Faculty of Medicine, University of Oslo, Oslo, Norway
| | - B A Robinson
- Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch, New Zealand
| | - H Morrin
- Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch, New Zealand
| | - J F Pearson
- Department of the Dean, University of Otago Christchurch, Christchurch, New Zealand
| | - J D Potter
- Wayne Francis Cancer Epidemiology Research Group, School of Health Sciences, University of Canterbury, Christchurch, New Zealand.,Centre for Public Health Research, Massey University, Wellington, New Zealand.,Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - M Paterson
- University of Canterbury Library, University of Canterbury, Christchurch, New Zealand
| | - H-M Surcel
- European Science Infrastructure Services, University of Oulu, Oulu, Finland
| | - E Pukkala
- Finnish Cancer Registry Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.,Faculty of Social Sciences, University of Tampere, Tampere, Finland
| | - M J Currie
- Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch, New Zealand
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11
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Tolušić Levak M, Mihalj M, Koprivčić I, Lovrić I, Novak S, Bijelić N, Baus-Lončar M, Belovari T, Kralik K, Pauzar B. Differential Expression of TFF Genes and Proteins in Breast Tumors. Acta Clin Croat 2018; 57:264-277. [PMID: 30431719 PMCID: PMC6532012 DOI: 10.20471/acc.2018.57.02.06] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
SUMMARY – The objective of this study was to determine differential expression of TFF1, TFF2 and TFF3 genes and proteins in breast tumor subtypes. In addition, we investigated the correlation between TFF genes within tumor subgroups, and TFF genes with clinical and pathologic characteristics of the tumor. Study group included 122 patients with surgically removed breast tumors. Samples were investigated using qRT-PCR and immunohistochemistry. TFF1 and TFF3 genes and proteins were expressed in breast tumors, while the levels of TFF2 gene and protein expression were very low or undetectable. TFF1 was significantly more expressed in benign tumors, while TFF3 was more expressed in malignant tumors. Gene and protein expression of both TFF1 and TFF3 was greater in lymph node-negative tumors, hormone positive tumors, tumors with moderate levels of Ki67 expression, and in grade II tumors. A strong positive correlation was found between TFF1 and TFF3 genes, and the expression of both negatively correlated with Ki67 and the level of tumor histologic differentiation. Our results suggest that TFF1 and TFF3, but not TFF2, may have a role in breast tumor pathogenesis and could be used in the assessment of tumor differentiation and malignancy.
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Affiliation(s)
| | - Martina Mihalj
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Ivan Koprivčić
- Department of Anatomy and Neuroscience, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.,Department of Surgery, Osijek University Hospital Centre, Osijek, Croatia
| | - Ivana Lovrić
- Department of Histology and Embryology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.,Department of Anatomy, Histology and Embryology, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Sanja Novak
- Department of Physiology and Immunology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Nikola Bijelić
- Department of Histology and Embryology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Mirela Baus-Lončar
- Department of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
| | - Tatjana Belovari
- Department of Histology and Embryology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Kristina Kralik
- Department of Medical Statistics and Informatics, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Biljana Pauzar
- Department of Histology and Embryology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.,Department of Clinical Cytology, Osijek University Hospital Centre, Osijek, Croatia
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12
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Yang R, Liang J, Xu GX, Ding LM, Huang HM, Su QZ, Yan J, Li YC. Human cytomegalovirus glycoprotein B inhibits migration of breast cancer MDA-MB-231 cells and impairs TGF-β/Smad2/3 expression. Oncol Lett 2018; 15:7730-7738. [PMID: 29849800 PMCID: PMC5962863 DOI: 10.3892/ol.2018.8344] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 12/06/2017] [Indexed: 02/07/2023] Open
Abstract
Breast cancer is a leading cause of cancer-associated mortality in females worldwide and evidence suggests that human cytomegalovirus (HCMV) infection may be implicated in the progress of breast cancer. HCMV glycoprotein B (gB) is the most abundant envelope protein and serves an important role in host cell entry. The present study aimed to clarify the role of HCMV gB in breast cancer cells. A HCMV gB construct (UL55) was generated and stable vUL55 gene lentivirus-transfected MDA-MB-231 cells were established. Subsequently, the effect of HCMV gB on the apoptosis and proliferation of MDA-MB-231 cells was measured by flow cytometry and Cell Counting Kit-8 assay. Furthermore, whether HCMV gB may modulate MDA-MB-231 cell migration was examined using Transwell and cell scratch assays. In addition, alterations in HCMV gB-modulated protein levels of transforming growth factor-β (TGF-β) and Mothers against decapentaplegic homologs 2/3 (Smad2/3) were detected using western blot analysis. The results indicated that UL55 cDNA was stably transfected into MDA-MB-231 cells, and that HCMV gB protein was stably expressed. No significant differences in cell apoptosis and proliferation between transfected (231-GB-OE) and negative control (231-NC) cells were observed, while the rate of cell migration was significantly decreased in the 231-GB-OE cells compared with the 231-NC cells. Additionally, the expression level of TGF-β and phosphorylation level of Smad2/3 were also decreased in 231-GB-OE cells compared with the 231-NC cells. Although certain previous studies indicated that HCMV infection was associated with breast carcinogenesis, the results of the present study indicate that the envelope protein HCMV gB exhibits no effect on cell apoptosis and proliferation, but inhibits breast cancer cell migration. This may be due to downregulated TGF-β/Smad signaling. Taken together, these studies may assist in developing anti-TGF-β agents that contribute to tumor suppression.
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Affiliation(s)
- Rui Yang
- Department of Laboratory Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China
| | - Jie Liang
- Institute of Immunology, University of Heidelberg, Heidelberg D-69120, Germany
| | - Guo-Xiong Xu
- Center Laboratory, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China
| | - Liu-Mei Ding
- Department of Laboratory Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China
| | - Hong-Mei Huang
- Department of Laboratory Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China
| | - Qi-Zhu Su
- Department of Laboratory Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China
| | - Jing Yan
- Department of Laboratory Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China
| | - Yun-Chun Li
- Department of Laboratory Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China
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13
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Bakhtiyrizadeh S, Hosseini SY, Yaghobi R, Safaei A, Sarvari J. Almost Complete Lack of Human Cytomegalovirus and Human papillomaviruses Genome in Benign and Malignant Breast Lesions in Shiraz, Southwest of Iran. Asian Pac J Cancer Prev 2017; 18:3319-3324. [PMID: 29286226 PMCID: PMC5980890 DOI: 10.22034/apjcp.2017.18.12.3319] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Breast cancer ranks as the most common cancer among women worldwide. There have been controversial reports regarding contributions of human papillomaviruses (HPVs) and human cytomegalovirus (HCMV) to its development. The aim of this study was to determine the frequency of HPV and HCMV positivity in benign and malignant breast tumors.
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Affiliation(s)
- Sahar Bakhtiyrizadeh
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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14
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Mikołajczyk A. Invited Brief Commentary on the Article "Breast Cancer Association with Cytomegalo Virus - a Tertiary Center Case-Control Study" Is Cytomegalo Virus a Breast Cancer Etiologic Risk Factor? J INVEST SURG 2017; 32:178-179. [PMID: 29260913 DOI: 10.1080/08941939.2017.1406019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Anita Mikołajczyk
- a Department of Public Health , Epidemiology and Microbiology, Faculty of Health Sciences, University of Warmia and Mazury in Olsztyn, ul. Warszawska 30, PL10-082 Olsztyn , Poland
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15
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Detection of Human Cytomegalovirus in Malignant and Benign Breast Tumors in Egyptian Women. Clin Breast Cancer 2017; 18:e629-e642. [PMID: 29396078 DOI: 10.1016/j.clbc.2017.10.018] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 09/19/2017] [Accepted: 10/31/2017] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Previous studies have reported a role for human cytomegalovirus (HCMV) in breast carcinogenesis. We sought to assess the role of HCMV infection in the development and/or progression of breast cancer (BC) among Egyptian patients. PATIENTS AND METHODS The study included 61 patients with BC cases. Of these 61 patients, 40 had been assessed for HCMV in the blood, BC tissue samples, and adjacent non-neoplastic tissue samples, and 21 had been assessed for HCMV in the tissue only. Tissue samples from 20 patients with fibroadenoma (FA) were also included. As a control group, 41 blood samples obtained from healthy women with no history of cancer were used as a blood control group. HCMV was assessed using enzyme-linked immunosorbent assay, real-time polymerase chain reaction (PCR), and immunohistochemistry (IHC). RESULTS A significant difference was found in the index value for the anti-CMV IgG antibodies between the BC patients and the control group (P = .001). Using real-time PCR, HCMV DNA was detected in 11 of 61 BC tissues (18%) compared with 1 of 20 FA tissues (5%). HCMV DNA was present in 8 of the 40 plasma samples (20%). Regarding the viral proteins, 21 of 61 samples (34.4%) were positive for early/immediate early (E/IE) and 49 (80.3%) were positive for PP65 expression by IHC. The concordance between the results obtained by the different assays was low. CMVPP65 expression was significantly associated with E/IE protein expression in the malignant and FA groups (P < .001). CONCLUSION The presence of CMV proteins and DNA in BC tissues suggests a role for this virus. However, the basic criteria to support a causal association of HCMV with BC were not fulfilled.
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16
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Mohammadizadeh F, Mahmudi F. Evaluation of human cytomegalovirus antigen expression in invasive breast carcinoma in a population of Iranian patients. Infect Agent Cancer 2017; 12:39. [PMID: 28670334 PMCID: PMC5485504 DOI: 10.1186/s13027-017-0148-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Accepted: 06/20/2017] [Indexed: 02/08/2023] Open
Abstract
Background The role of human cytomegalovirus (HCMV) in the development of breast carcinoma is questionable. The aim of this study was to evaluate the expression of the immediate early antigen (IE) of HCMV in breast carcinoma and its association with some clinicopathologic factors in a population of Iranian patients. Methods Formalin-fixed and paraffin-embedded tissue blocks from the pathology laboratories of the Azahra and Shahid Beheshti hospitals, Isfahan, Iran, from 2013 to 2016, were used in the study. We used immunohistochemistry and real-time PCR to detect the IE-antigen of HCMV in breast carcinoma, normal tissue adjacent to carcinoma, and normal tissue from mammoplasty specimens. Results A total of 96 samples were evaluated: 70 invasive breast carcinoma of different histologic subtypes and 26 mammoplasty normal breast tissues. All the samples were negative for IE-antigen expression. No relationship was seen between breast cancer and HCMV in this study. Conclusions The results of this study failed to show any relationship between HCMV and the development of breast carcinoma.
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Affiliation(s)
- Fereshteh Mohammadizadeh
- Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fatemeh Mahmudi
- Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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17
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Valle Oseguera CA, Spencer JV. Human cytomegalovirus interleukin-10 enhances matrigel invasion of MDA-MB-231 breast cancer cells. Cancer Cell Int 2017; 17:24. [PMID: 28228690 PMCID: PMC5307693 DOI: 10.1186/s12935-017-0399-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 02/08/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND While some risk factors for breast cancer are well-known, the influence of other factors, particularly virus infection, remains unclear. Human cytomegalovirus (HCMV) is widespread in the general population, and both molecular and epidemiological evidence has indicated links between HCMV and breast cancer. The HCMV protein cmvIL-10 is a potent suppressor of immune function that has also been shown to promote proliferation and migration of breast cancer cells. In this study, the impact of cmvIL-10 on tumor cell invasion through a simulated basement membrane was investigated. RESULTS MDA-MB-231 breast cancer cells exhibited invasion through a matrigel layer that was significantly enhanced in the presence of either purified cmvIL-10 or supernatants from HCMV-infected cells containing secreted cmvIL-10. Transcriptional profiling revealed that cmvIL-10 altered expression of several genes implicated in metastasis. Exposure to cmvIL-10 resulted in higher MMP-3 mRNA levels, greater protein expression, and increased enzymatic activity. Treatment with cmvIL-10 also increased expression of both urokinase plasminogen receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), which can stimulate MMP-3 activity and have previously been identified as poor prognostic markers in breast cancer patients. Finally, MDA-MB-231 cells treated with cmvIL-10 showed significant downregulation of metastasis suppressor 1 (MTSS1), a scaffolding protein that regulates cytoskeletal rearrangements and is frequently lost in metastatic tumors. CONCLUSIONS HCMV, and in particular the secreted viral cytokine, cmvIL-10, can induce cellular changes that facilitate cell migration and invasion. These findings indicate that HCMV may be associated with promoting the malignant spread of breast cancer cells and suggest that antiviral treatment may be a useful complement to chemotherapy in some patients.
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Affiliation(s)
- Cendy A Valle Oseguera
- Department of Biology, University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117 USA
| | - Juliet V Spencer
- Department of Biology, University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117 USA
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18
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Kumar A, Coquard L, Pasquereau S, Russo L, Valmary-Degano S, Borg C, Pothier P, Herbein G. Tumor control by human cytomegalovirus in a murine model of hepatocellular carcinoma. MOLECULAR THERAPY-ONCOLYTICS 2016; 3:16012. [PMID: 27626063 PMCID: PMC5008266 DOI: 10.1038/mto.2016.12] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Revised: 02/14/2016] [Accepted: 02/29/2016] [Indexed: 02/07/2023]
Abstract
Although viruses can cause cancer, other studies reported the regression of human tumors upon viral infections. We investigated the cytoreductive potential of human cytomegalovirus (HCMV) in a murine model of human hepatocellular carcinoma (HCC) in severe-immunodeficient mice. Infection of HepG2 cells with HCMV resulted in the absence of tumor or in a limited tumor growth following injection of cells subcutaneously. By contrast all mice injected with uninfected HepG2 cells and with HepG2 cells infected with UV-treated HCMV did develop tumors without any significant restriction. Analysis of tumors indicated that in mice injected with HCMV-infected-HepG2 cells, but not in controls, a restricted cellular proliferation was observed parallel to a limited activation of the STAT3-cyclin D1 axis, decreased formation of colonies in soft agar, and activation of the intrinsic apoptotic pathway. We conclude that HCMV can provide antitumoral effects in a murine model of HCC which requires replicative virus at some stages that results in limitation of tumor cell proliferation and enhanced apoptosis mediated through the intrinsic caspase pathway.
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Affiliation(s)
- Amit Kumar
- Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comté and COMUE Bourgogne Franche-Comté University, UPRES EA4266, SFR FED 4234, CHRU Besançon , Besançon, France
| | - Laurie Coquard
- Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comté and COMUE Bourgogne Franche-Comté University, UPRES EA4266, SFR FED 4234, CHRU Besançon , Besançon, France
| | - Sébastien Pasquereau
- Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comté and COMUE Bourgogne Franche-Comté University, UPRES EA4266, SFR FED 4234, CHRU Besançon , Besançon, France
| | - Laetitia Russo
- Department of Pathology, CHRU Besançon , Besançon, France
| | | | - Christophe Borg
- Department of Medical Oncology, INSERM UMR1098, EFS Bourgogne Franche-Comté , Besançon, France
| | - Pierre Pothier
- Department of Virology, Pathogens & Inflammation Laboratory, UPRES EA4266, SFR FED 4234, CHU Dijon , Dijon, France
| | - Georges Herbein
- Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comté and COMUE Bourgogne Franche-Comté University, UPRES EA4266, SFR FED 4234, CHRU Besançon , Besançon, France
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19
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Richardson AK, Currie MJ, Robinson BA, Morrin H, Phung Y, Pearson JF, Anderson TP, Potter JD, Walker LC. Cytomegalovirus and Epstein-Barr virus in breast cancer. PLoS One 2015; 10:e0118989. [PMID: 25723522 PMCID: PMC4344231 DOI: 10.1371/journal.pone.0118989] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 01/08/2015] [Indexed: 12/13/2022] Open
Abstract
Findings of polymerase chain reaction (PCR) studies of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) and breast cancer vary, making it difficult to determine whether either, both, or neither virus is causally associated with breast cancer. We investigated CMV and EBV in paired samples of breast cancer and normal breast tissue from 70 women using quantitative PCR. A serum sample from each woman was tested for CMV and EBV IgG. To place our results in context, we reviewed the existing literature and performed a meta-analysis of our results together with previous PCR studies of EBV, CMV, and breast cancer. Of the serology samples, 67 of 70 (96%) were EBV IgG positive and 49 of 70 (70%) were CMV IgG positive. QPCR detected EBV in 24 (34%) of the tumour and 9 (13%) of the paired normal specimens and CMV in 0 (0%) of the tumour and 2 (3%) of the paired normal specimens. Our findings, together with earlier results summarised in the meta-analysis, suggest several possibilities: variable findings may be due to limitations of molecular analyses; 'hit and run' oncogenesis may lead to inconsistent results; one or both viruses has a role at a later stage in breast cancer development; infection with multiple viruses increases breast cancer risk; or neither virus has a role. Future studies should focus on ways to investigate these possibilities, and should include comparisons of breast cancer tissue samples with appropriate normal tissue samples.
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Affiliation(s)
- Ann K. Richardson
- Wayne Francis Cancer Epidemiology Research Group, School of Health Sciences, University of Canterbury, Christchurch, New Zealand
- * E-mail:
| | - Margaret J. Currie
- Mackenzie Cancer Research Group, University of Otago, Christchurch, New Zealand
| | - Bridget A. Robinson
- Mackenzie Cancer Research Group, University of Otago, Christchurch, New Zealand
| | - Helen Morrin
- Mackenzie Cancer Research Group, University of Otago, Christchurch, New Zealand
| | - Yen Phung
- Mackenzie Cancer Research Group, University of Otago, Christchurch, New Zealand
| | - John F. Pearson
- Biostatistics and Computational Biology Unit, University of Otago, Christchurch, New Zealand
| | | | - John D. Potter
- Wayne Francis Cancer Epidemiology Research Group, School of Health Sciences, University of Canterbury, Christchurch, New Zealand
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America
- Centre for Public Health Research, Massey University, Wellington, New Zealand
| | - Logan C. Walker
- Mackenzie Cancer Research Group, University of Otago, Christchurch, New Zealand
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20
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Herbein G, Kumar A. The oncogenic potential of human cytomegalovirus and breast cancer. Front Oncol 2014; 4:230. [PMID: 25202681 PMCID: PMC4142708 DOI: 10.3389/fonc.2014.00230] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Accepted: 08/08/2014] [Indexed: 12/12/2022] Open
Abstract
Breast cancer is the leading causes of cancer-related death among women. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. Numerous articles indicate that breast tumors exhibit diverse phenotypes depending on their distinct physiopathological signatures, clinical courses, and therapeutic possibilities. The human cytomegalovirus (HCMV) is a multifaceted highly host specific betaherpesvirus that is regarded as asymptomatic or mildly pathogenic virus in immunocompetent host. HCMV may cause serious in utero infections as well as acute and chronic complications in immunocompromised individual. The involvement of HCMV in late inflammatory complications underscores its possible role in inflammatory diseases and cancer. HCMV targets a variety of cell types in vivo, including macrophages, epithelial cells, endothelial cells, fibroblasts, stromal cells, neuronal cells, smooth muscle cells, and hepatocytes. HCMV can be detected in the milk after delivery and thereby HCMV could spread to adjacent mammary epithelial cells. HCMV also infects macrophages and induces an atypical M1/M2 phenotype, close to the tumor-associated macrophage phenotype, which is associated with the release of cytokines involved in cancer initiation or promotion and breast cancer of poor prognosis. HCMV antigens and DNA have been detected in tissue biopsies of breast cancers and elevation in serum HCMV IgG antibody levels has been reported to precede the development of breast cancer in some women. In this review, we will discuss the potential role of HCMV in the initiation and progression of breast cancer.
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Affiliation(s)
- Georges Herbein
- Department of Virology and Department of Pathogens & Inflammation, UPRES EA4266, SFR FED 4234, CHRU Besançon, University of Franche-Comté , Besançon , France
| | - Amit Kumar
- Department of Virology and Department of Pathogens & Inflammation, UPRES EA4266, SFR FED 4234, CHRU Besançon, University of Franche-Comté , Besançon , France
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21
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Jha HC, Mittal A. Impact of viral and bacterial infections in coronary artery disease patients. World J Transl Med 2013; 2:49-55. [DOI: 10.5528/wjtm.v2.i3.49] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Accepted: 11/03/2013] [Indexed: 02/05/2023] Open
Abstract
Atherosclerosis is becoming an alarming disease for the existence of healthy human beings in the 21st century. There are a growing number of agents, either modernized life style generated, competitive work culture related or infection with some bacterial or viral agents, documented every year. These infectious agents do not have proper diagnostics or detection availability in many poor and developing countries. Hence, as active medical researchers, we summarize some aspects of infectious agents and their related mechanisms in this review which may be beneficial for new beginners in this field and update awareness in the field of cardiovascular biology.
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Alibek K, Kakpenova A, Mussabekova A, Sypabekova M, Karatayeva N. Role of viruses in the development of breast cancer. Infect Agent Cancer 2013; 8:32. [PMID: 24138789 PMCID: PMC3765990 DOI: 10.1186/1750-9378-8-32] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Accepted: 08/22/2013] [Indexed: 12/21/2022] Open
Abstract
The most common cancer worldwide among women is breast cancer. The initiation, promotion, and progression of this cancer result from both internal and external factors. The International Agency for Research on Cancer stated that 18-20% of cancers are linked to infection, and the list of definite, probable, and possible carcinogenic agents is growing each year. Among them, biological carcinogens play a significant role. In this review, data covering infection-associated breast and lung cancers are discussed and presented as possible involvements as pathogens in cancer. Because carcinogenesis is a multistep process with several contributing factors, we evaluated to what extent infection is significant, and concluded that members of the herpesvirus, polyomavirus, papillomavirus, and retrovirus families definitely associate with breast cancer. Detailed studies of viral mechanisms support this conclusion, but have presented problems with experimental settings. It is apparent that more effort needs to be devoted to assessing the role of these viruses in carcinogenesis, by characterizing additional confounding and synergistic effects of carcinogenic factors. We propose that preventing and treating infections may possibly stop or even eliminate certain types of cancers.
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Affiliation(s)
- Kenneth Alibek
- Nazarbayev University, 53 Kabanbay Batyr Avenue, Astana 010000, Kazakhstan
- National Medical Holding, 2 Syganak Street, Astana 010000, Kazakhstan
| | - Ainur Kakpenova
- Nazarbayev University, 53 Kabanbay Batyr Avenue, Astana 010000, Kazakhstan
| | - Assel Mussabekova
- Nazarbayev University, 53 Kabanbay Batyr Avenue, Astana 010000, Kazakhstan
| | - Marzhan Sypabekova
- Nazarbayev University, 53 Kabanbay Batyr Avenue, Astana 010000, Kazakhstan
| | - Nargis Karatayeva
- Nazarbayev University, 53 Kabanbay Batyr Avenue, Astana 010000, Kazakhstan
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