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Dr. Zongbing You received his MD at the age of 23 years and PhD at the age of 28 years from West China University of Medical Sciences, Chengdu, China. He is a tenured Associate Professor and Vice Chair for Research as well as Director of the Two-Year Research Master’s Degree Program in the Department of Structural and Cellular Biology at Tulane University School of Medicine, New Orleans, Louisiana, USA. He has published 80 publications and edited a professional book. His research interest is in inflammation and prostate cancer.
Th17 cells are a subset of T helper cells secreting interleukin-17 (IL-17A and IL-17F). We have systematically investigated the role of IL-17 in prostate cancer. We found that IL-17 receptor C (IL-17RC) expression was up-regulated in human prostatic intraepithelial neoplasia (PIN), hormone naïve prostate cancer, and castration-resistant prostate cancer. Using an Il-17rc;Pten (Phosphatase and tensin homolog) double knockout mouse model, we found that IL-17 promoted development of hormone-naïve and castration-resistant prostate cancer through multiple mechanisms, including: 1) directly stimulating expression of cytokines, chemokines, and growth factors; 2) directly inducing inflammatory cell infiltration; 3) increasing the ratio of immunosuppressive immune cells; 4) increasing angiogenesis; 5) enhancing cellular proliferation; and 6) inhibiting cellular apoptosis. Using an Mmp7;Pten double knockout mouse model, we found that MMP7 promoted prostate adenocarcinoma through induction of epithelial-to-mesenchymal transition (EMT). IL-17 induced MMP7 and EMT in human prostate cancer cell lines, while siRNA knockdown of MMP7 inhibited IL-17-induced EMT. Selective inhibitor of MMP7, inhibitor of Th17 cell differentiation, and anti-IL-17A neutralizing antibodies were able to partially inhibit prostate cancer formation in the Pten knockout mice. These findings demonstrate that IL-17-MMP7-EMT axis plays an important role in prostate cancer development, indicating IL-17-MMP7-EMT axis as a potential target for developing new strategies in the prevention and treatment of prostate cancer