TLR4 signaling promotes the expression of VEGF and TGFbeta1 in human prostate epithelial PC3 cells induced by lipopolysaccharide.

Chronic inflammation promotes tumor development and progression, and Toll-like receptors (TLRs) may play an important role in this process. In this study, we found that human prostate epithelial PC3 cells constitutively express TLR4 in mRNA and protein level. lipopolysaccharide (LPS) promotes the expression and secretion of immunosuppressive cytokine TGFbeta(1) and proangiogenic factor VEGF in human prostate epithelial PC3 cells. We further elucidated that functionally activation of TLR4 is essential for the increased VEGF and TGFbeta(1) mRNA expression in the cells. In addition, after LPS stimulation, the increased expression of NF-(K)B p65 protein was also detected in human PC3 cells. Our results demonstrate that TLR4 expressed on human PC3 cells is functionally active, and may play important roles in promoting prostate cancer immune escape, survival, progression, and metastasis by inducing immunosuppressive and proangiogenic cytokines.