Inflammatory mediators of prostate epithelial cells stimulated with Trichomonas vaginalis promote proliferative and invasive properties of prostate cancer cells

Abstract

Background Trichomonas vaginalis (Tv) is the most common sexually transmitted parasite. It is detected in prostatic tissue of benign prostatic hyperplasia, prostatitis, and prostate cancer (PCa) and has been suggested to cause chronic prostatitis. Moreover, up to 20% of all cancers worldwide are associated with chronic inflammation. Here, we investigated whether inflammatory mediators produced by normal human prostate epithelial cells (RWPE-1) stimulated with Tv could promote growth and invasiveness of PCa cells. Methods Conditioned medium of RWPE-1 cells was prepared by stimulating them with Tv (trichomonad-conditioned medium [TCM]) and without Tv (conditioned medium [CM]). Promotion of PCa cells (PC3, DU145, and LNCaP) was assessed by wound healing, proliferation, and invasion assays. Results We observed that the production of interleukin (IL)-1 beta, IL-6, CCL2, CXCL8, prostaglandin-E2 (PGE(2)), and COX2 by RWPE-1 cells was increased by stimulating them with Tv. When PCa cells were incubated with TCM, their proliferation, invasion, and migration increased. Moreover, they showed increased epithelial-mesenchymal transition (EMT)-related markers by a reduction in epithelial markers and an increase in mesenchymal markers. In vivo, xenograft tumor tissues injected with TCM also showed increased expression of cyclin D1 and proliferating cell nuclear antigen, as well as induction of EMT. Receptors and signal molecules of PCa cells increased in response to exposure to TCM, and blocking receptors (CXCR1, CXCR2, C-C chemokine receptor 2, glycoprotein 130, EP2, and EP4) reduced the proliferation of PCa cells with decreased production of cytokines (CCL2, IL-6, and CXCL8) and PGE(2), and expression of NF-kappa B and Snail1. CONCLUSIONS Our results suggest that Tv infection may be one of the factors creating the supportive microenvironment to promote proliferation and invasiveness of PCa cells.