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Chen TP, Lee HL, Huang YH, Hsieh MJ, Chiang WL, Kuo WH, Chou MC, Yang SF, Yeh CB. Association of intercellular adhesion molecule-1 single nucleotide polymorphisms with hepatocellular carcinoma susceptibility and clinicopathologic development. Tumour Biol 2015; 37:2067-74. [PMID: 26341495 DOI: 10.1007/s13277-015-3992-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 08/25/2015] [Indexed: 12/19/2022] Open
Abstract
Intercellular adhesion molecule-1 (ICAM-1) is a human protein encoded by the ICAM-1 gene and is typically expressed on endothelial cells and immune cells. ICAM-1 is associated with episode, growth, invasion, and metastasis of hepatocellular carcinoma (HCC). However, the association between ICAM-1 genetic variants and the risk of HCC is undetermined. In this study, we investigated the potential associations of ICAM-1 single nucleotide polymorphisms (SNPs) with susceptibility to HCC and its clinicopathological characteristics. A total of 918 participants, including 613 controls participants and 305 patients with HCC, were selected for the analysis of ICAM-1 SNPs (rs3093030, rs5491, rs281432, and rs5498) by using real-time PCR genotyping. After adjusting for covariants of age, sex, and alcohol consumption, 125 smoker patients with HCC carrying at least one G genotype (AG and GG) in rs5498 were observed to have a higher HCC risk compared with 231 smoker control participants carrying the wild-type allele AA (adjusted odds ratio (AOR), 1.713; 95 % confidence interval (CI), 1.091-2.690; P = 0.019). However, patients who possess at least one polymorphic allele of rs5498 are less prone to develop vascular invasive (AOR, 0.309; 95 % CI, 0.103-0.926; P = 0.036). The results suggest that the genetic polymorphism in ICAM-1 rs5498 SNPs with genotype AG and GG is associated with HCC risk among smokers. Moreover, gene and environment interactions of ICAM-1 rs5498 polymorphisms might alter susceptibility to liver cancer. Therefore, ICAM-1 rs5498 may serve as a marker to predict the vascular invasion risk in smoker patients with HCC.
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Affiliation(s)
- Tsung-Po Chen
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Hsiang-Lin Lee
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yu-Hui Huang
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Ming-Ju Hsieh
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan
| | - Whei-Ling Chiang
- School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
| | - Wu-Hsien Kuo
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Ming-Chih Chou
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chao-Bin Yeh
- Department of Emergency Medicine, School of Medicine, Chung Shan Medical University, 110, Section 1, Chien-Kuo N. Road, Taichung, Taiwan. .,Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
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McNally RS, Davis BK, Clements CM, Accavitti-Loper MA, Mak TW, Ting JPY. DJ-1 enhances cell survival through the binding of Cezanne, a negative regulator of NF-kappaB. J Biol Chem 2010; 286:4098-106. [PMID: 21097510 DOI: 10.1074/jbc.m110.147371] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Heightened DJ-1 (Park7) expression is associated with a reduction in chemotherapeutic-induced cell death and poor prognosis in several cancers, whereas the loss of DJ-1 function is found in a subgroup of Parkinson disease associated with neuronal death. This study describes a novel pathway by which DJ-1 modulates cell survival. Mass spectrometry shows that DJ-1 interacts with BBS1, CLCF1, MTREF, and Cezanne/OTUD7B/Za20d1. Among these, Cezanne is a known deubiquitination enzyme that inhibits NF-κB activity. DJ-1/Cezanne interaction is confirmed by co-immunoprecipitation of overexpressed and endogenous proteins, maps to the amino-terminal 70 residues of DJ-1, and leads to the inhibition of the deubiquitinating activity of Cezanne. Microarray profiling of shRNA-transduced cells shows that DJ-1 and Cezanne regulate IL-8 and ICAM-1 expression in opposing directions. Similarly, DJ-1 enhances NF-κB nuclear translocation and cell survival, whereas Cezanne reduces these outcomes. Analysis of mouse Park7(-/-) primary cells confirms the regulation of ICAM-1 by DJ-1 and Cezanne. As NF-κB is important in cellular survival and transformation, IL-8 functions as an angiogenic factor and pro-survival signal, and ICAM-1 has been implicated in tumor progression, invasion, and metastasis; these data provide an additional modality by which DJ-1 controls cell survival and possibly tumor progression via interaction with Cezanne.
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Affiliation(s)
- R Sean McNally
- Department of Microbiology-Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7295, USA
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Matsuoka S, Matsumura H, Arakawa Y, Nakamura H, Nirei K, Yamagami H, Ogawa M, Nakajima N, Amaki S, Tanaka N, Moriyama M. Expression of intercellular adhesion molecule-1 in the livers of rats treated with diethylnitrosamine. J Clin Biochem Nutr 2009; 45:137-43. [PMID: 19794920 PMCID: PMC2735624 DOI: 10.3164/jcbn.08-247] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2008] [Accepted: 01/31/2009] [Indexed: 11/22/2022] Open
Abstract
It has been reported that levels of soluble intercellular adhesion molecule-1 (ICAM-1) in the blood are elevated in hepatocellular carcinoma patients. In the present study, serial observations of the localization of ICAM-1 in the liver were made by light and electron microscopy in rats with carcinogen-induced cancer. Male Fisher rats were given diethylnitrosamine (DEN) orally in their drinking water. Rats were sacrificed at 6, 8, 12, or 14 weeks after the start of DEN administration and the liver tissue was collected. ICAM-1 expression in liver was assessed using indirect immunoperoxidase staining with anti-rat ICAM-1 antibody. Although ICAM-1 expression by endothelial cells in livers of DEN-treated rats was lower than in the control group at 8 weeks, it was higher in the membrane and cytoplasm of hepatocytes. The expression of ICAM-1 in mesenchymal cells was decreased, paralleling development of cellular atypia, whereas in hepatocyte membranes and cytoplasm it was increased in these atypia. ICAM-1 was localized to the cytoplasm of cancer cells, but to the membrane of hepatocytes in the treated livers at 14 weeks. Furthermore, the levels of ICAM-1 in mesenchymal cells tended to be lower in the cancerous area than in the atypical hyperplastic nodule, and were reduced as the density of cell atypia increased, in comparison to cells in areas without cancerous nodules. We concluded that ICAM-1 may be influenced the development of cancer induced in the rat liver by a chemical carcinogen.
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Affiliation(s)
- Shunichi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan
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4
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Xu J, Mei MH, Zeng SE, Shi QF, Liu YM, Qin LL. Expressions of ICAM-1 and its mRNA in sera and tissues of patients with hepatocellular carcinoma. World J Gastroenterol 2001; 7:120-5. [PMID: 11819746 PMCID: PMC4688687 DOI: 10.3748/wjg.v7.i1.120] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- J Xu
- 95 Leque Road, Department of Hepatobiliary Surgery, Guilin Medical College, Guilin 541001, Guangxi, China.
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Mei MH, Xu J, Shi QF, Yang JH, Chen Q, Qin LL. Clinical significance of serum intercellular adhesion molecule-1 detection in patients with hepatocellular carcinoma. World J Gastroenterol 2000; 6:408-410. [PMID: 11819611 PMCID: PMC4688765 DOI: 10.3748/wjg.v6.i3.408] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Velikova G, Banks RE, Gearing A, Hemingway I, Forbes MA, Preston SR, Hall NR, Jones M, Wyatt J, Miller K, Ward U, Al-Maskatti J, Singh SM, Finan PJ, Ambrose NS, Primrose JN, Selby PJ. Serum concentrations of soluble adhesion molecules in patients with colorectal cancer. Br J Cancer 1998; 77:1857-63. [PMID: 9667659 PMCID: PMC2150349 DOI: 10.1038/bjc.1998.309] [Citation(s) in RCA: 66] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.
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Affiliation(s)
- G Velikova
- ICRF Cancer Medicine Research Unit, St James's University Hospital, Leeds, UK
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Velikova G, Banks RE, Gearing A, Hemingway I, Forbes MA, Preston SR, Jones M, Wyatt J, Miller K, Ward U, Al-Maskatti J, Singh SM, Ambrose NS, Primrose JN, Selby PJ. Circulating soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with gastric cancer. Br J Cancer 1997; 76:1398-404. [PMID: 9400933 PMCID: PMC2228185 DOI: 10.1038/bjc.1997.569] [Citation(s) in RCA: 49] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 45 patients with gastric cancer before treatment and their correlation with clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology, survival and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with gastric cancer in comparison with the group of healthy subjects (P < 0.00001 and P < 0.0001 respectively). Increased serum concentrations of VCAM-1 were associated with locally advanced and metastatic disease whereas ICAM-1 was significantly elevated both in local and in advanced/metastatic disease. Soluble E-cadherin and E-selectin concentrations did not show any significant elevation in gastric cancer patients. Concentrations of soluble adhesion molecules showed significant correlation with each other (except E-selectin and VCAM-1) and with alkaline phosphatase. Soluble ICAM-1 and VCAM-1 were significantly associated with an elevated total white cell count. Patients with elevated VCAM-1 had significantly poorer survival in comparison with patients with normal serum levels (P = 0.0361).
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Affiliation(s)
- G Velikova
- ICRF Cancer Medicine Research Unit, St James's University Hospital, Leeds, UK
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Mathew J, Hines JE, Obafunwa JO, Burr AW, Toole K, Burt AD. CD44 is expressed in hepatocellular carcinomas showing vascular invasion. J Pathol 1996. [PMID: 8691349 DOI: 10.1002/(sici)1096-9896(199605)179:1%3c74::aid-path531%3e3.0.co;2-e] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
CD44 and its variant isoforms are a group of transmembrane glycoproteins which play important roles in immune recognition, in lymphocyte trafficking, and in cell-cell and cell-matrix interactions. Although CD44 is expressed by some normal human epithelial and mesenchymal cells, upregulation of CD44 expression has been related to the metastatic potential of some malignant tumours. In this study of 27 hepatocellular carcinomas (HCCs), an indirect immunohistochemical method was used to investigate the distribution of CD44 in normal liver and to determine whether expression of the standard form of CD44 (CD44s), or two of its variant isoforms (CD44-v3 and CD44-v6), correlated with tumour grade, proliferation indices, or histological evidence of vascular invasion. Fifteen of the tumours were Edmondson grade II, four were grade III, and eight were grade IV. Liver cell dysplasia was present in adjacent liver parenchyma in three cases and vascular invasion was observed in ten HCCs. Vascular invasion was found to be more frequent in high grade HCCs and a significant correlation was observed between tumour proliferation indices and vascular invasion. CD44s was not expressed by epithelial cells of normal liver but was expressed by tumour cells in six HCCs; vascular invasion was present in five of these HCCs. Three CD44s-positive cases also expressed CD44-v3 and two of these also expressed CD44-v6. CD44 was not expressed in areas of hepatocyte dysplasia. There was a significant correlation between CD44 expression and the presence of vascular invasion, but not between CD44 expression and tumour grade or tumour proliferation indices. It is concluded that upregulation of cell surface CD44 expression on malignant hepatocytes is related to their tendency to vascular invasion and may have implications relating to metastasis and prognosis in patients with HCCs.
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Affiliation(s)
- J Mathew
- University Department of Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, U.K
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9
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Abstract
CD44 and its variant isoforms are a group of transmembrane glycoproteins which play important roles in immune recognition, in lymphocyte trafficking, and in cell-cell and cell-matrix interactions. Although CD44 is expressed by some normal human epithelial and mesenchymal cells, upregulation of CD44 expression has been related to the metastatic potential of some malignant tumours. In this study of 27 hepatocellular carcinomas (HCCs), an indirect immunohistochemical method was used to investigate the distribution of CD44 in normal liver and to determine whether expression of the standard form of CD44 (CD44s), or two of its variant isoforms (CD44-v3 and CD44-v6), correlated with tumour grade, proliferation indices, or histological evidence of vascular invasion. Fifteen of the tumours were Edmondson grade II, four were grade III, and eight were grade IV. Liver cell dysplasia was present in adjacent liver parenchyma in three cases and vascular invasion was observed in ten HCCs. Vascular invasion was found to be more frequent in high grade HCCs and a significant correlation was observed between tumour proliferation indices and vascular invasion. CD44s was not expressed by epithelial cells of normal liver but was expressed by tumour cells in six HCCs; vascular invasion was present in five of these HCCs. Three CD44s-positive cases also expressed CD44-v3 and two of these also expressed CD44-v6. CD44 was not expressed in areas of hepatocyte dysplasia. There was a significant correlation between CD44 expression and the presence of vascular invasion, but not between CD44 expression and tumour grade or tumour proliferation indices. It is concluded that upregulation of cell surface CD44 expression on malignant hepatocytes is related to their tendency to vascular invasion and may have implications relating to metastasis and prognosis in patients with HCCs.
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Affiliation(s)
- J Mathew
- University Department of Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, U.K
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Marui A, Fukuda Y, Koyama Y, Nakano I, Urano F, Yamada M, Hayakawa T. Serum levels of soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in liver disease, and their changes by treatment with interferon. J Int Med Res 1996; 24:258-65. [PMID: 8725986 DOI: 10.1177/030006059602400304] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured by an enzyme-linked immunosorbent assay in patients with chronic hepatitis (n = 57), liver cirrhosis (n = 19) and hepatocellular carcinoma (n = 33). Serum levels of sICAM-1 and sVCAM-1 were significantly higher in liver disease than those in controls (P < 0.0001 and P < 0.0005, respectively). A total of 22 patients with chronic hepatitis C were treated with interferon. Pretreatment levels of sICAM-1 and sVCAM-1 were not significantly different between complete responders and non-responders. In complete responders, serum sICAM-1 and sVCAM-1 levels 1 year after interferon treatment significantly decreased compared to the pretreatment levels (P < 0.005 and P < 0.05, respectively). Post-treatment levels of sICAM-1 and sVCAM-1 in complete responders were also significantly lower than those in non-responders (P < 0.005 and P < 0.05, respectively). This suggests that monitoring soluble adhesion molecules might be useful in the follow-up of patients with liver disease.
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Affiliation(s)
- A Marui
- Second Department of Internal Medicine, Nagoya University School of Medicine, Japan
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Mizoi T, Ohtani H, Suzuki Y, Shiiba K, Matsuno S, Nagura H. Intercellular adhesion molecule-1 expression by macrophages in human gastrointestinal carcinoma: possible roles as host immune/inflammatory reaction. Pathol Int 1995; 45:565-72. [PMID: 7496501 DOI: 10.1111/j.1440-1827.1995.tb03504.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Tumor-associated macrophages (TAM) are one of the factors which modulate the carcinoma progression. The present study described immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) in stromal cells in human gastrointestinal carcinoma identifying the cell types by immunoelectron microscopy. In colon and gastric carcinomas, ICAM-1-positive cells were mostly stromal cells, and major cell types were identified as macrophages and fibroblasts by immunoelectron microscopy. Macrophages were characterized by their ovoid shape, cytoplasmic projections, abundant vacuoles, phagocytosis, and paucity of rough endoplasmic reticulum. Fibroblasts contained stacks of rough endoplasmic reticulum. Macrophages were major cells among ICAM-1-positive cells along the invasive margin, while fibroblasts were predominant in the stroma within carcinoma in colon and intestinal-type gastric carcinomas. Lymphocytes positive for lymphocyte function associated antigen (LFA-1), a counter-receptor of ICAM-1, were densely distributed along the invasive margin, and sparsely in the stroma within carcinoma. In diffuse-type gastric carcinoma, most macrophages were dendritic-shaped and negative for ICAM-1. Our study suggests that the invasive margin is an area similar to active inflammation, where the antigen presenting cells (macrophages) and lymphocytes may interact via the ICAM-1/LFA-1 adhesion.
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Affiliation(s)
- T Mizoi
- Department of Pathology, Tohoku University, School of Medicine, Sendai, Japan
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Jiang WG, Puntis MC, Hallett MB. Molecular and cellular basis of cancer invasion and metastasis: implications for treatment. Br J Surg 1994; 81:1576-90. [PMID: 7827878 DOI: 10.1002/bjs.1800811107] [Citation(s) in RCA: 87] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
In the past decade significant advances in establishing the underlying biological mechanisms of tumour invasion and metastasis have been made. Some of the triggering factors and genes relevant to metastatic spread have been identified. Advances have also been made in understanding the signal transduction pathways involved in invasion and metastasis. This increased comprehension of the malignant metastatic process has enabled new antimetastatic strategies to be devised. This review summarizes progress in these areas and discusses the implications for the treatment of metastasis.
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Affiliation(s)
- W G Jiang
- Department of Surgery, University of Wales College of Medicine, Health Park, Cardiff, UK
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