Interleukin-17 promotes development of castration-resistant prostate cancer potentially through creating an immunotolerant and pro-angiogenic tumor microenvironment
Article
BACKGROUND; Interleukin-17 (IL-17) has been demonstrated to promote formation and growth of hormone-naive prostate adenocarcinoma in mice. IL-17's role in development of castration-resistant prostate cancer is unknown. In the present study, we investigated IL-17's role in castration-resistant prostate cancer in a mouse model.; METHODS; IL-17 receptor C (IL-17RC) deficient mice were interbred with Pten conditional mutant mice to produce RC+ mice that maintained IL-17RC expression and RC- mice that were IL-17RC deficient. Male RC+ and RC- mice were Pten-null and were castrated at 16 weeks of age when invasive prostate cancer had already formed. At 30 weeks of age, all male mice were analyzed for the prostate phenotypes.; RESULTS; RC- mice displayed prostates that were smaller than RC+ mice. Approximately 23% of prostatic glands in RC- mice, in contrast to 65% of prostatic glands in RC+ mice, developed invasive adenocarcinomas. Compared to castrate RC+ mice, castrate RC- mouse prostate had lower rates of cellular proliferation and higher rates of apoptosis as well as lower levels of MMP7, YBX1, MTA1, and UBE2C proteins. In addition, castrate RC- mouse prostate had less angiogenesis, which was associated with decreased levels of COX-2 and VEGF. Moreover, castrate RC- mouse prostate had fewer inflammatory cells including lymphocytes, myeloid-derived suppressor cells, and macrophages.; CONCLUSIONS; Taken together, our findings suggest that IL-17 promotes development of invasive prostate adenocarcinomas under castrate conditions, potentially through creating an immunotolerant and pro-angiogenic tumor microenvironment. Prostate 74:869-879, 2014. (c) 2014 Wiley Periodicals, Inc.
