High C-X-C motif chemokine5 expression is associated with malignant phenotypes of prostate cancer cells via autocrine and paracrine pathways.

Abstract

The present study aimed to examine the effects and mechanisms of exogenous C-X-C motif chemokine5(CXCL5) and lentiviral CXCL5 overexpression on the regulation of malignant behaviors of prostate cancer cells invitro and in a nude mouse xenograft model. The expression levels of CXCL5 and a number of tumor-related genes were assessed by using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, ELISA, or immunohistochemistry in normal and cancerous prostate cells and tissues. Cell proliferation, colony formation, and Transwell assays were performed to determine the effects of exogenous, autocrine, and paracrine CXCL5 on prostate cancer cell proliferative and migratory capacity. The results indicated that CXCL5 expression was upregulated in PC‑3 and DU145 prostate cancer cells, in WPMY‑1 normal prostate stromal cells, and in RWPE‑1 prostate epithelial cells, as well as in prostate cancer tissue specimens. Exogenous CXCL5 exposure resulted in increase in prostate cancer cell proliferation, colony formation, and migration. In cells transfected with a CXCL5 overexpression vector, in cells cultured in conditioned medium from CXCL5-overexpressing WPMY cells, and in cells co-cultured with CXCL5‑OE WPMY cells prostate cancer cell malignant phenotypes were induced in an autocrine/paracrine fashion invitro; similar results were observed in nude mouse xenografts. CXCL5 overexpression also regulated expression of tumor-related genes, including BAX, N-Myc downstream-regulated gene3, extracellular signal-regulated kinase1/2, C-X-C chemokine receptor type 2, interleukin18, Bcl‑2, and caspase‑3. These data demonstrated that CXCL5 expression was upregulated in prostate cancer tissues and that exogenous CXCL5 protein exposure or CXCL5 overexpression promoted malignant phenotypes of prostate cancer cells invitro and invivo.