Abstract 5199: Promotion of prostate cancer cell migration and invasion via CXCR3 signaling

Abstract

Abstract Tumor cells exist within, and cross-communicate with their local milieu that includes non-neoplastic cells using a variety of soluble chemokines. CXCR3-binding chemokines have recently been implicated in breast cancer metastasis, though inversely correlated with prostate tumor growth. There are two CXCR3 isoforms differing by a 5′ splice variant, that vary in their distribution, with CXCR3A found mainly on cells of the hematopoietic lineage and CXCR3B the predominant species on adherent cells. These isoforms vary in their predilection for the four common ligands, and the consequences of signaling through these different isoforms can be divergent. How these two isoforms inform tumorigenesis and invasion still remains unclear. Here, we examined the expression and function of the two different variants of CXCR3 in prostate cancer cells. In contrast to normal prostate epithelial cells (RWPE-1), in which CXCR3B was the primary splice variant, CXCR3A was highly expressed in two tested prostate cancer cell lines (DU-145 and PC-3). Two known ligands of CXCR3, CXCL10/IP10 and CXCL11/IP9/I-TAC, were down-regulated in these two prostate cancer cell lines, while the CXCR3B-selective ligand CXCL4/PF4 was overexpressed, allowing for autocrine stimulation. Instead of inhibiting cell migration as in RWPE-1 cells, CXCL4/PF4 and CXCL10/IP10 promoted cell motility and invasiveness in both DU-145 and PC-3 cells in vitro, which might be a result of PLCβ3 activation. Overexpression of CXCR3B in DU-145 cells slightly decreased cell chemoattractant movement and invasion. These data suggest that the aberrant expression of CXCR3A and down-regulation of CXCR3B may promote prostate tumor metastasis via stimulating cell migration. (Funded by a VA Merit Award) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5199.