Background: Expression of the inflammatory chemokine CCL5 (RANTES) by tumor cells is thought to correlate with the progression of several cancers. CCL5 was shown to induce breast cancer cell migration, mediated by the receptor CCR5. A CCR5 antagonist was demonstrated to inhibit experimental breast tumor growth. Recently, CCL5 and CCR5 mRNA expression was reported in prostate cancer (PCa) tissues. Herein, we characterized CCL5 and CCR5 expression in cultures of PCa cells and explored possible functions of CCL5 in PCa progression.
Methods: Quantitative RT-PCR, ELISA, and immunohistochemical staining were performed to examine CCL5 expression in prostate cell lines. CCR5 expression was measured by flow cytometry. Proliferation and invasion assays were performed to determine potential functions of CCL5 and CCR5 in PCa.
Results: Expression of CCL5 mRNA and protein was found in human PCa cell lines (PC-3; DU-145; LNCaP) and primary prostate adenocarcinoma cells. CCL5 and CCR5 were also detected in human PCa tissues. CCR5 expression was demonstrated on the cell surface of PCa cells, as well as in intracellular pools. Incubation with CCL5 (10-100 ng/ml) induced PCa cell proliferation, and the CCR5 antagonist TAK-779 inhibited CCL5-induced proliferation. CCL5 was found to stimulate PCa cell invasion, and TAK-779 blocked the effects of CCL5.
Conclusions: In light of evidence that inflammation influences the pathogenesis of PCa, these results suggest that inflammatory chemokines, such as CCL5, expressed by prostate cells may act directly on the growth and survival of PCa cells. Chemokine receptor antagonists may thus block autocrine mechanisms of PCa progression.