CXCR3 in Carcinoma Progression

Overview

Journal Histol Histopathol

Specialties Anatomy & Histology
Pathology

Date 2015 Feb 10

PMID 25663474

Citations 39

Authors

Bo Ma

Ahmad Khazali

Alan Wells

Affiliations

Soon will be listed here.

Abstract

CXCR3 is a G-protein coupled receptor which binds to ELR-negative CXC chemokines that have been found to impact immune responses, vascular develop, and wound repair. More recently, CXCR3 has been examined in the context of cancer and increased expression in many human tumors has been correlated with poor prognosis in breast, melanoma, colon and renal cancer patients. Three variants of CXCR3 are identified so far (CXCR3-A, CXCR3-B and CXCR3-alt) with the two primary ones, CXCR3-A and CXCR3-B, considered to induce opposite physiological functions. Generally, CXCR3-A, the predominant form in hematopoietic cells, appears to mediate tumor "go" signaling via promoting cell proliferation, survival, chemotaxis, invasion and metastasis; while CXCR3-B, the main form on formed elements including epithelial cells, appears to mediate tumor "stop" signaling via promoting growth suppression, apoptosis and vascular involution. Thus, aberrant expression of the isoforms CXCR3-A and CXCR3-B could affect tumor progression. In this review, we have discussed the profiles of CXCR3 variants and related signaling, as well as the role of CXCR3 variants in cancer.

Citing Articles

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References

Monteagudo C, Martin J, Jorda E, Llombart-Bosch A . CXCR3 chemokine receptor immunoreactivity in primary cutaneous malignant melanoma: correlation with clinicopathological prognostic factors. J Clin Pathol. 2006; 60(6):596-9. PMC: 1955073. DOI: 10.1136/jcp.2005.032144. View

Datta D, Flaxenburg J, Laxmanan S, Geehan C, Grimm M, Waaga-Gasser A . Ras-induced modulation of CXCL10 and its receptor splice variant CXCR3-B in MDA-MB-435 and MCF-7 cells: relevance for the development of human breast cancer. Cancer Res. 2006; 66(19):9509-18. DOI: 10.1158/0008-5472.CAN-05-4345. View

Xanthou G, Williams T, Pease J . Molecular characterization of the chemokine receptor CXCR3: evidence for the involvement of distinct extracellular domains in a multi-step model of ligand binding and receptor activation. Eur J Immunol. 2003; 33(10):2927-36. DOI: 10.1002/eji.200324235. View

Mueller A, Meiser A, McDonagh E, Fox J, Petit S, Xanthou G . CXCL4-induced migration of activated T lymphocytes is mediated by the chemokine receptor CXCR3. J Leukoc Biol. 2008; 83(4):875-82. DOI: 10.1189/jlb.1006645. View

Chao Y, Wu Q, Acquafondata M, Dhir R, Wells A . Partial mesenchymal to epithelial reverting transition in breast and prostate cancer metastases. Cancer Microenviron. 2011; 5(1):19-28. PMC: 3343195. DOI: 10.1007/s12307-011-0085-4. View

Du C, Yao Y, Xue W, Zhu W, Peng Y, Gu J . The expression of chemokine receptors CXCR3 and CXCR4 in predicting postoperative tumour progression in stages I-II colon cancer: a retrospective study. BMJ Open. 2014; 4(8):e005012. PMC: 4139647. DOI: 10.1136/bmjopen-2014-005012. View

Andersson A, Yang S, Huang M, Zhu L, Kar U, Batra R . IL-7 promotes CXCR3 ligand-dependent T cell antitumor reactivity in lung cancer. J Immunol. 2009; 182(11):6951-8. DOI: 10.4049/jimmunol.0803340. View

Goldberg-Bittman L, Neumark E, Sagi-Assif O, Azenshtein E, Meshel T, Witz I . The expression of the chemokine receptor CXCR3 and its ligand, CXCL10, in human breast adenocarcinoma cell lines. Immunol Lett. 2004; 92(1-2):171-8. DOI: 10.1016/j.imlet.2003.10.020. View

Loetscher M, Loetscher P, Brass N, Meese E, Moser B . Lymphocyte-specific chemokine receptor CXCR3: regulation, chemokine binding and gene localization. Eur J Immunol. 1998; 28(11):3696-705. DOI: 10.1002/(SICI)1521-4141(199811)28:11<3696::AID-IMMU3696>3.0.CO;2-W. View

10.

Cambien B, Karimdjee B, Richard-Fiardo P, Bziouech H, Barthel R, Millet M . Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism. Br J Cancer. 2009; 100(11):1755-64. PMC: 2695685. DOI: 10.1038/sj.bjc.6605078. View

11.

Struyf S, Burdick M, Proost P, Van Damme J, Strieter R . Platelets release CXCL4L1, a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis. Circ Res. 2004; 95(9):855-7. DOI: 10.1161/01.RES.0000146674.38319.07. View

12.

Wells A, Grahovac J, Wheeler S, Ma B, Lauffenburger D . Targeting tumor cell motility as a strategy against invasion and metastasis. Trends Pharmacol Sci. 2013; 34(5):283-9. PMC: 3640670. DOI: 10.1016/j.tips.2013.03.001. View

13.

Walser T, Rifat S, Ma X, Kundu N, Ward C, Goloubeva O . Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res. 2006; 66(15):7701-7. DOI: 10.1158/0008-5472.CAN-06-0709. View

14.

Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L . An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med. 2003; 197(11):1537-49. PMC: 2193908. DOI: 10.1084/jem.20021897. View

15.

Kawada K, Hosogi H, Sonoshita M, Sakashita H, Manabe T, Shimahara Y . Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes. Oncogene. 2007; 26(32):4679-88. DOI: 10.1038/sj.onc.1210267. View

16.

Fulton A . The chemokine receptors CXCR4 and CXCR3 in cancer. Curr Oncol Rep. 2009; 11(2):125-31. DOI: 10.1007/s11912-009-0019-1. View

17.

Amatschek S, Lucas R, Eger A, Pflueger M, Hundsberger H, Knoll C . CXCL9 induces chemotaxis, chemorepulsion and endothelial barrier disruption through CXCR3-mediated activation of melanoma cells. Br J Cancer. 2010; 104(3):469-79. PMC: 3049560. DOI: 10.1038/sj.bjc.6606056. View

18.

Aksoy M, Yang Y, Ji R, Reddy P, Shahabuddin S, Litvin J . CXCR3 surface expression in human airway epithelial cells: cell cycle dependence and effect on cell proliferation. Am J Physiol Lung Cell Mol Physiol. 2005; 290(5):L909-18. DOI: 10.1152/ajplung.00430.2005. View

19.

Furuya M, Yoneyama T, Miyagi E, Tanaka R, Nagahama K, Miyagi Y . Differential expression patterns of CXCR3 variants and corresponding CXC chemokines in clear cell ovarian cancers and endometriosis. Gynecol Oncol. 2011; 122(3):648-55. DOI: 10.1016/j.ygyno.2011.05.034. View

20.

Johrer K, Zelle-Rieser C, Perathoner A, Moser P, Hager M, Ramoner R . Up-regulation of functional chemokine receptor CCR3 in human renal cell carcinoma. Clin Cancer Res. 2005; 11(7):2459-65. DOI: 10.1158/1078-0432.CCR-04-0405. View