T helper 17 (Th17) cells secret interleukin-17A (IL-17A) and interleukin-17F. Th17 cells and IL-17A are increased in prostate tumors. The role of IL-17A in prostate cancer is not clear. The objective of this in-vitro study was to investigate the effects of IL-17A on prostatic epithelial cells. Cell growth assay, Western blot, and real-time quantitative reverse transcription- polymerase chain reaction (qRT-PCR) analysis were used to measure the effects of IL-17A on the immortalized normal human prostatic epithelial cell lines (RWPE-1 and pRNS-1-1), human high-grade prostatic intraepithelial neoplasia (PIN) cell line, human prostate cancer LNCaP cell line, and mouse prostate cancer TRAMP-C1 cell line. We found that recombinant human IL-17A (20 ng/ml) did not affect cell growth rate in any of the prostatic cell lines studied. IL-17A did not significantly activate Nuclear Factor-kappaB (NF-kappaB) or Extracellular signal-Regulated Kinase (ERK) signaling pathway in RWPE-1, pRNS-1-1, or PIN cells. IL-17A activated NF-kappaB and/or ERK signaling pathways in LNCaP and TRAMP-C1 cells. When IL-17RC (receptor of IL-17A) was overexpressed in PIN and LNCaP cells, activation of NF-kappaB or ERK signaling pathway by IL-17A was significantly enhanced. IL-17A modestly induced mRNA expression of chemokines (CXCL1 and CXCL2) in RWPE-1, pRNS-1-1, and PIN cells. IL-17A induced mRNA expression of chemokines (CXCL1, CXCL2, CCL2, CCL5, CCL7, and CCL20) and cytokine IL-6 in LNCaP cells. In mouse TRAMP-C1 cells, IL-17A induced mRNA expression of chemokines (CXCL1, CXCL2, CXCL5, CCL2, and CCL5) and cytokine IL-6. When IL-17RC was overexpressed in PIN and LNCaP cells, chemokine expression was significantly enhanced. Our findings suggest that although IL-17A has no effects on cell growth in-vitro, it may modulate the stroma-epithelial interaction in tumor microenvironment in-vivo via stimulation of expression of chemokines and cytokines.

Acknowledgement: DoD W81XWH-05-1-0567, NIH/NCRR 2P20 RR020152-06, and LCRC Fund.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1436.