• CXCR4/CXCL12
• Chemokines
• Immunohistochemistry
• Pancreatic ductal adenocarcinoma

• Humans
• Carcinoma, Pancreatic Ductal
• Pancreatic Neoplasms
• Receptors, CXCR4
• Tumor Microenvironment
• Biomarkers, Tumor

• CXCR4-CXCL12-CXCR7 axis
• chemokine receptor
• immune checkpoint PD-1/PD-L1
• outcome
• pancreatic adenocarcinoma (PDAC)
• pancreatic cancer prognosis
• pancreatic resection
• tumor microenvironment (TME)

• Humans
• B7-H1 Antigen
• Biomarkers, Tumor
• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/pathology
• Carcinoma, Pancreatic Ductal/surgery
• Chemokine CXCL12
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/surgery
• Prognosis
• Programmed Cell Death 1 Receptor
• Receptors, CXCR
• Receptors, CXCR4

• Apoptosis
• CXCR7
• carotenoid
• fucoxanthinol
• hamster pancreatic cancer

• Adenocarcinoma/drug therapy
• Animals
• Carcinogenesis
• Carcinoma, Pancreatic Ductal/drug therapy
• Cricetinae
• Disease Models, Animal
• Female
• Humans
• beta Carotene/analogs & derivatives
• beta Carotene/pharmacology
• beta Carotene/therapeutic use

• Immunotherapy
• Pancreatic cancer

• Carcinoma, Pancreatic Ductal/drug therapy
• Humans
• Immunotherapy
• Pancreatic Neoplasms/drug therapy
• Tumor Microenvironment
• Pancreatic Neoplasms

CXCL12 and its receptors have been extensively studied in cancer, including their influence on cancer stem cells (CSCs) and their niche. This intensive research has led to a better understanding of the crosstalk between CXCL12 and CSCs, which has aided in designing several drugs that are currently being tested in clinical trials. However, a comprehensive review has not been published to date. The aim of this review is to provide an overview on how CXCL12 axes are involved in the regulation and maintenance of CSCs, their presence and influence at different cellular levels within the CSC niche, and the current state-of-the-art of therapeutic approaches aimed to target the CXCL12 crossroads.

Cancer stem cells (CSCs) are defined as a subpopulation of “stem”-like cells within the tumor with unique characteristics that allow them to maintain tumor growth, escape standard anti-tumor therapies and drive subsequent repopulation of the tumor. This is the result of their intrinsic “stem”-like features and the strong driving influence of the CSC niche, a subcompartment within the tumor microenvironment that includes a diverse group of cells focused on maintaining and supporting the CSC. CXCL12 is a chemokine that plays a crucial role in hematopoietic stem cell support and has been extensively reported to be involved in several cancer-related processes. In this review, we will provide the latest evidence about the interactions between CSC niche-derived CXCL12 and its receptors—CXCR4 and CXCR7—present on CSC populations across different tumor entities. The interactions facilitated by CXCL12/CXCR4/CXCR7 axes seem to be strongly linked to CSC “stem”-like features, tumor progression, and metastasis promotion. Altogether, this suggests a role for CXCL12 and its receptors in the maintenance of CSCs and the components of their niche. Moreover, we will also provide an update of the therapeutic options being currently tested to disrupt the CXCL12 axes in order to target, directly or indirectly, the CSC subpopulation.

• CSC niche
• CXCL12
• CXCR4
• CXCR4 inhibitors
• cancer stem cells

Pancreatic ductal adenocarcinoma (PDAC) is one of the malignancies with the highest morality rate due to postoperative local invasion and distant metastasis. Although C-X-C motif chemokine receptor (CXCR) subunits have been reported as prognostic indicators in gastric cancer, the prognostic value of CXCR subunits in PDAC remains poorly understood. In the present study, the expression levels and biological functions of CXCR subunits were investigated using multiple publicly accessible bioinformatic platforms and databases. Survival analysis was used to evaluate the prognostic value of CXCR subunits in 112 early-stage PDAC cases by setting the median expression levels as the cut-off values. A nomogram was constructed to combine CXCR subunit expression levels and clinical data for prognosis prediction. Moreover, the association between CXCR subunit expression levels and tumor infiltration levels were detected in PDAC. The expression levels of CXCR subunits were elevated in PDAC tumor tissues. In the multivariate Cox proportional risk regression model, high CXCR2, CXCR4 and CXCR6 expression levels in early-stage PDAC were associated with a more favorable prognosis. Further, it was demonstrated that the differential expression levels of CXCR subunits in PDAC for combined survival analysis could contribute to risk stratification. The nomogram model demonstrated the contribution of CXCR subunits and clinical features in the prognosis of PDAC. Gene Set Enrichment Analysis suggested that CXCR subunits serve a role in immunomodulatory functions. The expression levels and somatic copy number alterations of CXCR subunits were associated with tumor infiltration levels in PDAC. CXCR subunits were associated with prognosis in patients with early-stage PDAC and may be potential drug targets for the treatment of pancreatic cancer.

• CXCR
• PDAC
• immune infiltration
• survival analysis

Chemokine (C-X-C motif) receptor 7 (CXCR7), recently termed ACKR3, belongs to the G protein-coupled cell surface receptor family, binds to stromal cell-derived factor-1 [SDF-1, or chemokine (C-X-C motif) ligand 12] or chemokine (C-X-C motif) ligand 11, and is the most common chemokine receptor expressed in a variety of cancer cells. SDF-1 binds to its receptor chemokine (C-X-C motif) receptor 4 (CXCR4) and regulates cell proliferation, survival, angiogenesis and migration. In recent years, another new receptor for SDF-1, CXCR7, has been discovered, and CXCR7 has also been found to be expressed in a variety of tumor cells and tumor-related vascular endothelial cells. Many studies have shown that CXCR7 can promote the growth and metastasis of a variety of malignant tumor cells. Unlike CXCR4, CXCR7 exhibits a slight modification in the DRYLAIV motif and does not induce intracellular Ca²⁺ release following ligand binding, which is essential for recruiting and activating G proteins. CXCR7 is generally thought to work in three ways: (1) Recruiting β-arrestin 2; (2) Heterodimerizing with CXCR4; and (3) Acting as a “scavenger” of SDF-1, thus lowering the level of SDF-1 to weaken the activity of CXCR4. In the present review, the expression and role of CXCR7, as well as its prognosis in cancers of the digestive system, were investigated.

• Stromal cell-derived factor-1
• Chemokine (C-X-C motif) receptor 7
• Chemokine (C-X-C motif) receptor 4
• Carcinoma
• Digestive system

In China the incidence and mortality rates of colon cancer have been increasing annually. Studies have revealed that CXCR7 is expressed in many tumors. The aim of the present study was to investigate the function of CXCR7 in colon cancer. The expression level of chemokine receptor 7 (CXCR7) in Caco-2 and HCT116 cells was investigated to elucidate the effect of CXCR7 on cell biological behavior. Reverse transcription-quantitative PCR and western blot analysis were used to detect the expression level of CXCR7 in Caco-2 and HCT116 cells after transfection with small interfering (si)RNA. To analyze the in vitro biological function of CXCR7, cell proliferation was measured using a Cell Counting Kit-8 assay, and cell invasion and migration were measured using Matrigel, and Transwell and wound healing assays. siRNAs were successfully transfected into Caco-2 and HCT116 cells and resulted in a decrease in CXCR7 protein and mRNA expression. Downregulation of CXCR7 inhibited Caco-2 and HCT116 cell proliferation, invasion, and migration. Regulation of CXCR7 expression may affect the biological behavior of Caco-2 and HCT116 cells, suggesting that CXCR7 has a potential role in molecular therapy in colon cancer.

• CXCR7
• biological behaviors of neoplasms
• colon
• gene expression

CXC chemokine receptor 7 (CXCR7) is a G-protein-coupled receptor that signals through the β-arrestin pathway. Its ligands include interferon-inducible T cell α chemoattractant (CXCL11) and stromal cell-derived factor-1 (CXCL12). It interacts with CXCR4, and the two are associated with various cancers, as well as other disease states such as coronary artery disease, stroke, inflammation and human immunodeficiency virus (HIV). Antibodies and small interfering RNA (siRNA) have shown the utility of antagonists of CXCR7 in these disease states. Although some small molecules were initially reported as antagonists due to their displayed activity, many function as agonists while still producing the desired pharmacologic effects. A potential reason for this contradiction is that effects may be due to elevated extracellular CXCL12 levels.

• CXCL12
• CXCR4
• CXCR7

• CXCR4
• Immunohistochemistry
• Pancreatic adenocarcinoma
• Pancreatic neuroendocrine tumour
• Somatostatin receptor

• Adenocarcinoma/genetics
• Adenocarcinoma/metabolism
• Adenocarcinoma/mortality
• Adenocarcinoma/pathology
• Adult
• Aged
• Biomarkers
• Cell Line, Tumor
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Intestinal Neoplasms/genetics
• Intestinal Neoplasms/metabolism
• Intestinal Neoplasms/mortality
• Intestinal Neoplasms/pathology
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Neuroendocrine Tumors/genetics
• Neuroendocrine Tumors/metabolism
• Neuroendocrine Tumors/mortality
• Neuroendocrine Tumors/pathology
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Receptors, CXCR4/genetics
• Receptors, CXCR4/metabolism
• Somatostatin/genetics
• Somatostatin/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology

• CXCL12
• CXCR4
• Marker
• Meta-analysis
• PDAC
• Pancreatic ductal adenocarcinoma
• Prognosis

CXC chemokine receptor 7 (CXCR7) is frequently overexpressed in a variety of tumors. Nevertheless, whether CXCR7 can be used as a tumor prognosis marker has not been systematically assessed. The current meta-analysis was performed to obtain an accurate evaluation of the relationship between CXCR7 level and the prognosis of cancer patients.

Embase, Web of Science, and PubMed were systematically searched according to a defined search strategy up to June 11, 2018. Then, the required data were extracted from all qualified studies which were screened out based on the defined inclusion and exclusion criteria. Finally, the hazard ratios (HR) with 95% confidence intervals (CI) were used to evaluate the prognostic significance of CXCR7 in tumor patients.

A total of 28 original research studies comprising 33 cohorts and 5685 patients were included in this meta-analysis. The results showed that CXCR7 overexpression was significantly related to worse overall survival (OS) (HR 1.72; 95% CI 1.49–1.99), disease-free survival (DFS) (HR 5.58; 95% CI 3.16–9.85), progression-free survival (PFS) (HR 2.83; 95% CI 1.66–4.85) and recurrence-free survival (RFS) (HR 1.58; 95% CI 1.34–1.88) in cancer patients. Furthermore, for certain types of cancer, significant associations between higher CXCR7 expression and worse OS of glioma (HR 1.77; 95% CI 1.43–2.19), breast cancer (HR 1.45; 95% CI 1.28–1.63), esophageal cancer (HR 2.72; 95% CI 1.11–6.66) and pancreatic cancer (HR 1.46; 95% CI 1.12–1.90) were found. However, for lung cancer and hepatocellular cancer, there was no significant relationship between CXCR7 expression level and OS, (HR 2.40; 95% CI 0.34–17.07) and (HR 1.37; 95% CI 0.84–2.24) respectively.

Increased CXCR7 level could predict poor prognosis of tumor patients and might be regarded as a novel prognostic biomarker for tumor patients.

• CXCR7
• Cancer
• Meta-analysis
• Prognosis

Chemokine (C-X-C motif) receptor 7 (CXCR7) and its ligand, chemokine (C-X-C motif) ligand 12 (CXCL12), were established to be involved in biological behaviors and associated with prognosis in many cancers. However, effects, underlying mechanisms of CXCL12-CXCR7 axis in invasive phenotype of pancreatic cancer (PC) and its clinicopathologic significances have not been comprehensively explored. In the present study, it was first found by tissue microarray-based immunohistochemistry that CXCL12 and CXCR7 staining scores were significantly associated with vessel invasion and overall survival in two independent cohorts of PC. Besides, co-expression of these proteins was an independent prognosticator in multivariate analysis in both cohorts. Then, migration and invasion, but not proliferation, were decreased in CXCR7-stably silenced PC cells, whereas opposite changes were observed in CXCR7-stably overexpressed cells, accompanied by alterations of mTOR and Rho/ROCK pathways. CXCL12 stimulated migration, invasion, CXCR7 expression and phosphorylation of key mTOR proteins. AMD3100 did not influence effects of CXCL12. Two mTOR inhibitors, rapamycin and Torin1, reversed enhanced invasive phenotypes and mTOR phosphorylation in CXCR7-overexpressed cells. Moreover, CXCR7 directly interacts with mTOR. Finally, liver metastasis, but not growth, was affected by CXCR7 status in orthotopically-implanted PC models in nude mice. Collectively, CXCL12-CXCR7 axis accelerates migration and invasion of PC cells through mTOR and Rho/ROCK pathways, and predicts poor prognosis of PC.

• CXCL12
• CXCR7
• invasive phenotype
• mTOR
• pancreatic cancer
• prognosis

Background: Follicular thyroid carcinoma's (FTC) often benign course is partially due to adjuvant radioactive iodine (RAI) treatment. However, once the tumour has spread and fails to retain RAI, the therapeutic options are limited and the outcome is poor. In this subset of patients, the identification of novel druggable biomarkers appears invaluable. Here, we investigated the stage dependent expression and functional role of the C-X-C chemokine receptors type 4 and 7 (CXCR4/7) in FTC.

Methods: CXCR4/7 expression was examined in 44 FTC and corresponding non-neoplastic thyroid specimens as well as 10 FTC distant metastases and 18 follicular adenomas using tissue microarray technology. Expression levels were correlated with clinicopathological variables as well as overall and recurrence free survival. Changes regarding cell cycle activation, tumour cell invasiveness and mRNA expression of genes related to epithelial-mesenchymal transition (EMT) were investigated after treatment with recombinant human SDF1α/CXCL12 (rh-SDF1α) and CXCR4 antagonists AMD3100 and WZ811.

Results: CXCR4/7 expression was associated with large tumour size, advanced UICC stage as well as shorter overall and recurrence free survival. CXCR4 was significantly higher expressed in distant metastases than in primary tumour cores. In addition, rh-SDF1α induced invasive growth, cell cycle activation and EMT, while CXCR4 antagonists significantly reduced FTC invasiveness in vitro.

Conclusion: Here we provide first evidence of the biological importance of the CXCR4/CXCR7/CXCL12 axis in FTC. Our findings underscore the therapeutic potential of this chemokine receptor family in advanced FTC and offer new valuable insight into the oncogenesis of metastatic FTC.

• CXCL12
• CXCR4
• CXCR7
• FTC
• metastasis

Medullary thyroid carcinoma (MTC) is a rare and challenging endocrine malignancy. Once spread, the therapeutic options are limited and the outcome poor. For these patients, the identification of new druggable biological markers is of great importance. Here, we investigated the prognostic and biological role of the C-X-C chemokine receptors type 4 and 7 (CXCR4/7) in MTC.

Eighty-six MTC and corresponding non-neoplastic thyroid specimens were immunohistochemically stained for CXCR4/7 using tissue microarray technology and expression levels correlated with clinicopathological variables. Medullary thyroid carcinoma cell line TT was treated with recombinant human SDF1α/CXCL12 (rh-SDF1α) and CXCR4 antagonists AMD3100 and WZ811. Changes in cell cycle activation, tumour cell invasiveness as well as changes in mRNA expression levels of genes associated with epithelial–mesenchymal transition (EMT) were investigated.

High CXCR4 expression was associated with large tumour size and metastatic disease. CXCR4 antagonists significantly reduced tumour cell invasiveness, while the treatment with rh-SDF1α stimulated invasive growth, caused cell cycle activation and induced EMT.

The CXCR4/CXCR7/CXCL12 axis plays an important role in MTC. We provide first evidence that the chemokine receptors might serve as potential therapeutic targets in patients with advanced MTC and offer new valuable insight into the underlying molecular machinery of metastatic MTC.

Chemokines are involved in many aspects of oncogenesis, including regulation of cancer cell growth, dissemination and host-tumor response. However, the potential of the chemokine receptors, CXCR4 and CXCR7, in serving as biomarkers in extramammary Paget's disease (EMPD) has been rarely examined. Expressions of CXCR4 and CXCR7 were evaluated in 92 EMPD specimens by immunohistochemistry. High expression of CXCR4 and CXCR7 were both correlated with regional lymph node metastasis and presence of lymphovascular invasion. High expression of CXCR7 also correlated with the depth of invasion. The prognostic value of these two chemokines were also investigated in progression-free survival (PFS) and cancer-specific survival (CSS). Both high expression of CXCR4 and CXCR7 were indicative of shorter PFS and CSS. In the combined prognostic model, concomitant high expression of CXCR4 and CXCR7 were suggestive of poor prognosis compared with the other two groups. In the multivariate analysis, depth of invasion, combined prognostic model and regional lymph node metastasis at diagnosis were the independent prognostic factors for EMPD patients for PFS, and the former two factors independently impacted CSS. Our results demonstrated that CXCR4 and CXCR7 can be used as prognostic biomarkers and prediction of aggressiveness of EMPD. Therapy targeting CXCR4 and CXCR7 may helpful to prevent EMPD progression and improve the prognosis of EMPD.

• CXCR4
• CXCR7
• EMPD
• invasive
• prognosis.

Pancreatic cancer is a lethal disease with a propensity for invading and metastasizing into the surrounding tissues, including the liver and intestines. A number of factors are aberrantly overexpressed in this tumor type and actively promote cancer progression and metastasis. The present study demonstrates that paired box transcription factor 6 (PAX6) and C-X-C chemokine receptor 4 (CXCR4) are frequently co-expressed in primary pancreatic adenocarcinoma tumors and established cell lines. Expression analysis methods used in the present study included evaluation of protein expression by western blot analysis and immunofluorescence, transcript expression levels by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and luciferase assays utilizing regulatory elements from the CXCR4 gene locus. Canonical PAX6 and alternative splice variant PAX6(5a) proteins are expressed in pancreatic cancer and can drive gene expression through a conserved enhancer element within the first intron of the CXCR4 gene. As demonstrated by the introduction of an exogenous reporter construct with or without the intronic enhancer, loss of this element inhibited gene expression within numerous pancreatic cancer cell lines including Panc1, MIA-PaCa2 and BxPC3. All of the pancreatic cancer cell lines expressed the canonical CXCR4B transcript in addition to the alternatively spliced variant CXCR4A as determined by RT-qPCR experiments. The discovery of variant transcripts in pancreatic cancer cells may provide new candidates for future targeted therapies.

• C-X-C chemokine receptor 4
• CXCR4 transcript variant A
• CXCR4 transcript variant B
• PAX6 exon 5 alternative transcript variant
• alternative splice variants
• paired box transcription factor 6
• pancreatic cancer

• CXCR7
• laryngeal cancer
• maxillary sinus carcinoma
• nasal polyposis

• CXCL12
• CXCR4
• CXCR7
• Schwann cells
• pancreatic cancer

C-X-C chemokine receptor 4 (CXCR4) is frequently over-expressed in various types of cancer; many agents against CXCR4 are in clinical development currently despite variable data for the prognostic impact of CXCR4 expression. Here eighty-five studies with a total of 11,032 subjects were included to explore the association between CXCR4 and progression-free survival (PFS) or overall survival (OS) in subjects with cancer. Pooled analysis shows that CXCR4 over-expression is significantly associated with poorer PFS (HR 2.04; 95% CI, 1.72-2.42) and OS (HR=1.94; 95% CI, 1.71-2.20) irrespective of cancer types. Subgroup analysis indicates significant association between CXCR4 and shorter PFS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, renal cancer, gynecologic cancer, pancreatic cancer and liver cancer; the prognostic effects remained consistent across age, risk of bias, levels of adjustment, median follow-up period, geographical area, detection methods, publication year and size of studies. CXCR4 over-expression predicts unfavorable OS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, head and neck cancer, renal cancer, lung cancer, gynecologic cancer, liver cancer, prostate cancer and gallbladder cancer; these effects were independence of age, levels of adjustment, publication year, detection methods and follow-up period. In conclusion, CXCR4 over-expression is associated with poor prognosis in cancer.

• CXCR4
• cancer
• meta-analysis
• prognostic biomarker
• survival

• CXC chemokine receptor 7
• cervical intraepithelial neoplasia
• immunohistochemistry
• receiver operating characteristics curve analysis

• C-X-C motif receptor 7
• chemokine receptor
• gastrointestinal neoplasm
• therapeutic target
• tumorigenesis

• Biomarkers, Tumor/metabolism
• Carcinoma, Pancreatic Ductal/diagnosis
• Carcinoma, Pancreatic Ductal/metabolism
• Carcinoma, Pancreatic Ductal/mortality
• Humans
• Kaplan-Meier Estimate
• Multivariate Analysis
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/mortality
• Prognosis
• Proportional Hazards Models
• Receptors, CXCR4/metabolism

Aim of this study was to assess the biological function in tumor progression and metastatic process carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1, 5 and 6 in pancreatic adenocarcinoma (PDAC).

CEACAM knock down cells were established and assessed in vitro and in a subcutaneous and intraperitoneal mouse xenograft model. Tissue and serum expression of patients with PDAC were assessed by immunohistochemistry (IHC) and by enzyme linked immunosorbent assays.

Presence of lymph node metastasis was correlated with CEACAM 5 and 6 expression (determined by IHC) and tumor recurrence exclusively with CEACAM 6. Patients with CEACAM 5 and 6 expression showed a significantly shortened OS in Kaplan-Meier survival analyses. Elevated CEACAM6 serum values showed a correlation with distant metastasis and. Survival analysis revealed a prolonged OS for patients with low serum CEACAM 1 values. In vitro proliferation and migration capacity was increased in CEACAM knock down PDAC cells, however, mice inoculated with CEACAM knock down cells showed a prolonged overall-survival (OS). The number of spontaneous pulmonary metastasis was increased in the CEACAM knock down group.

The effects mediated by CEACAM expression in PDAC are complex, though overexpression is correlated with loco-regional aggressive tumor growth. However, loss of CEACAM can be considered as a part of epithelial-mesenchymal transition and is therefore of rather importance in the process of distant metastasis.

• Adult
• Aged
• Aged, 80 and over
• Animals
• Antigens, CD/genetics
• Antigens, CD/metabolism
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Carcinoembryonic Antigen/genetics
• Carcinoembryonic Antigen/metabolism
• Cell Adhesion Molecules/genetics
• Cell Adhesion Molecules/metabolism
• Cell Line, Tumor
• Female
• GPI-Linked Proteins/genetics
• GPI-Linked Proteins/metabolism
• Gene Knockdown Techniques
• Heterografts
• Humans
• Lung Neoplasms/metabolism
• Lung Neoplasms/secondary
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Neoplasm Transplantation
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• Survival Analysis

• Biomarker
• Erlotinib
• Gemcitabine
• Human equilibrative nucleoside transporter 1
• KRAS
• Nab-paclitaxel
• Pancreatic cancer
• SMAD4
• SPARC
• p53

• Animals
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Carcinoma, Pancreatic Ductal/drug therapy
• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/metabolism
• Carcinoma, Pancreatic Ductal/pathology
• Humans
• Molecular Targeted Therapy
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• Precision Medicine
• Predictive Value of Tests
• Signal Transduction
• Translational Research, Biomedical

• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic/therapeutic use
• Biomarkers, Tumor/analysis
• CA-19-9 Antigen/blood
• Capecitabine
• Carcinoembryonic Antigen/blood
• Carcinoma, Pancreatic Ductal/blood
• Carcinoma, Pancreatic Ductal/chemistry
• Carcinoma, Pancreatic Ductal/mortality
• Carcinoma, Pancreatic Ductal/pathology
• Carcinoma, Pancreatic Ductal/therapy
• Chemoradiotherapy, Adjuvant/methods
• Chemoradiotherapy, Adjuvant/mortality
• Deoxycytidine/analogs & derivatives
• Deoxycytidine/therapeutic use
• Female
• Fluorouracil/analogs & derivatives
• Fluorouracil/therapeutic use
• Genes, ras/genetics
• Hepatocyte Growth Factor/blood
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms/blood
• Pancreatic Neoplasms/chemistry
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/therapy
• Pancreaticoduodenectomy
• Prognosis
• Prospective Studies
• Proto-Oncogene Proteins/analysis
• Proto-Oncogene Proteins p21(ras)
• Proton Therapy/methods
• Receptors, CXCR/analysis
• ras Proteins/analysis

• P01 CA021239 NCI NIH HHS
• P01-CA021239 NCI NIH HHS
• P01-CA80124 NCI NIH HHS
• R01 CA159258 NCI NIH HHS
• R01-CA159258 NCI NIH HHS
• C06 CA059267 NCI NIH HHS
• P01 CA080124 NCI NIH HHS
• C06-CA059267 NCI NIH HHS

• Astrocytoma/genetics
• Astrocytoma/metabolism
• Astrocytoma/pathology
• Brain Neoplasms/genetics
• Brain Neoplasms/metabolism
• Brain Neoplasms/pathology
• Carcinogenesis
• Gene Expression Regulation, Neoplastic
• Glioblastoma/genetics
• Glioblastoma/metabolism
• Glioblastoma/pathology
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit/genetics
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• Immunohistochemistry
• Isocitrate Dehydrogenase/genetics
• Isocitrate Dehydrogenase/metabolism
• Kaplan-Meier Estimate
• Mutation/genetics
• Neoplasm Grading
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Receptors, CXCR/genetics
• Receptors, CXCR/metabolism
• Receptors, CXCR4/genetics
• Receptors, CXCR4/metabolism
• Up-Regulation

• CXCL12
• CXCR4
• CXCR7
• Extracellular loops
• GPCR
• HIV-1

• 9,10-Dimethyl-1,2-benzanthracene
• Animals
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Carcinogenesis/genetics
• Carcinogenesis/metabolism
• Carcinogenesis/pathology
• Cell Line, Tumor
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Molecular Sequence Annotation
• Oligonucleotide Array Sequence Analysis
• Pancreas/metabolism
• Pancreas/pathology
• Pancreatic Neoplasms/chemically induced
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• Pancreatitis, Acute Necrotizing/chemically induced
• Pancreatitis, Acute Necrotizing/genetics
• Pancreatitis, Acute Necrotizing/metabolism
• Pancreatitis, Acute Necrotizing/pathology
• Pancreatitis, Chronic/chemically induced
• Pancreatitis, Chronic/genetics
• Pancreatitis, Chronic/metabolism
• Pancreatitis, Chronic/pathology
• Rats
• Rats, Sprague-Dawley
• Receptors, CXCR/genetics
• Receptors, CXCR/metabolism
• Ubiquitin-Conjugating Enzymes/genetics
• Ubiquitin-Conjugating Enzymes/metabolism
• Pancreatic Neoplasms

The biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors, which include epidermal growth factor receptor agonists and members of the transforming growth factor β family. Furthermore, the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small, immunomodulatory proteins also play key roles in carcinogenesis and may, therefore, be potential targets for novel therapeutic approaches. In this review, we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.

• Chemokine
• Receptor
• Signal transduction
• Tumor progression
• Targeted therapeutics
• Digestive system
• Cancer

• Animals
• Cell Transformation, Neoplastic/immunology
• Cell Transformation, Neoplastic/pathology
• Chemokines/metabolism
• Digestive System/immunology
• Digestive System/pathology
• Digestive System Neoplasms/immunology
• Digestive System Neoplasms/pathology
• Digestive System Neoplasms/therapy
• Humans
• Receptors, Chemokine/metabolism
• Signal Transduction

Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The aim of this study was to evaluate the prognostic impact of the expression of the chemokine SDF-1 and its receptors CXCR4 and CXCR7 in patients with renal cell carcinoma.

The expression of CXCR4, CXCR7 and SDF-1 in specimens from 97 renal cell carcinoma patients was evaluated by immunohistochemistry on a tissue microarray. These results were correlated with the clinicopathological parameters and survival of the patients.

CXCR4 and CXCR7 were expressed in all patients, whereas SDF-1 was expressed in 61 patients (62.9%). No association was observed between the expression of CXCR4, CXCR7 or SDF-1 and the clinical or pathological data except between SDF-1 expression and Fuhrman’s grade (P = 0.015). Patients with high expression of CXCR4, CXCR7 and SDF-1 had shorter overall survival and recurrence-free survival than those with low expression. In a multivariate analysis, the high expression of CXCR4, CXCR7 and SDF-1 correlated with poor overall survival and recurrence-free survival independent of gender, age, AJCC stage, lymph node status, metastasis, histologic variant and Fuhrman’s grade.

High levels of CXCR4, CXCR7 and SDF-1 were associated with poor overall survival and recurrence-free survival in renal cell carcinoma patients. CXCR4, CXCR7 and SDF-1 may serve as useful prognostic markers and therapeutic targets for renal cell carcinoma.