Abstract 1648: Interleukin-6 expression is restricted to the prostate stromal compartment and is not expressed by either primary or metastatic prostatic adenocarcinoma cells

Background: Interleukin-6 (IL-6) is a pleiotropic cytokine that elicits multiple physiological processes including immune responses, hematopoiesis, and cellular proliferation and differentiation. IL-6 has also been implicated in a number of pathophysiologic processes, including carcinogenesis. Multiple studies suggest that IL-6 may contribute to the development and/or progression of prostate cancer, and high systemic levels of IL-6 are associated with a more aggressive clinical course. A number of studies have indicated that prostatic adenocarcinoma cells express IL-6; yet, the source of IL-6 production in the prostate tumor microenvironment is debatable and it remains unclear if the cytokine acts in an autocrine or paracrine manner. Understanding the cellular origin of IL-6 is essential to establishing the mechanistic basis by which IL-6 may promote prostate cancer progression. Methods: Quantitative PCR (qPCR) and chromogenic in situ hybridization (CISH) were used to study IL-6 expression in primary clinical prostatic carcinomas. As an initial approach, RNA derived from 11 prostate cell lines and 10 matched benign and tumor frozen prostate tissue samples were analyzed for IL-6 expression by qPCR. Next, formalin-fixed, paraffin embedded (FFPE) samples from the 11 cell lines, 21 prostatectomy samples, and 12 metastatic prostate cancer biopsy or autopsy tissue samples were analyzed by chromogenic in situ hybridization (CISH) for IL-6 mRNA (RNAscope, Advanced Cell Diagnostics, Inc.). Results: Three of the prostate cell lines (PrSC, RWPE, DU145) were found to be positive for IL-6 expression by both qPCR and CISH, indicating complete concordance between the two assays. Surprisingly, qPCR analyses revealed that benign prostate tissues most often had higher expression of IL-6 than matched tumor. Subsequent IL-6 CISH analysis indicated that prostate adenocarcinoma cells do not express IL-6 mRNA in either primary or metastatic cancer cells; rather, IL-6 mRNA expression was nearly exclusively restricted to the prostate stromal compartment and was highly up-regulated in areas of acute inflammation and prostatic atrophy. Conclusions: Our results are in contrast to published literature that argues that prostate cancer cells are the origin of IL-6 in the prostate tumor microenvironment and that prostate cancer progression is mediated by autocrine IL-6 signaling. The restriction of IL-6 expressing cells primarily to the prostate stromal compartment may alter the current understanding of how IL-6 may mediate the development and progression of prostate cancer. Citation Format: Shu-Han Yu, Qizhi Zheng, Jun Luo, Anne Macgregor-Das, Emmanuel S. Antonarakis, Angelo M. De Marzo, Karen Sfanos. Interleukin-6 expression is restricted to the prostate stromal compartment and is not expressed by either primary or metastatic prostatic adenocarcinoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1648. doi:10.1158/1538-7445.AM2014-1648