CXCR3 in carcinoma progression.

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.