Abstract
Background: African American men (AAM) have a 60% higher risk of being diagnosed with prostate cancer and a 2 to 3 times greater risk of dying from the disease compared to European American men (EAM). We previously reported evidence that there may be a molecular basis for these disparities from high-throughput gene expression analysis of PCa specimens, the data showed that pro-inflammatory cytokine signaling factors, including IL6 and TGFB1, are significantly upregulated and over-represented in PCa from AAM.
Objective/Methods: the objective of our more recent research was to gain understanding of the role for IL6 in promoting aggressive prostate cancer in AAM. We used established cell lines derived from PCa from AAM and EAM to study if cancer cells produce IL6 and how IL6 impacts cancer cell phenotypes in vitro. We also conducted a pilot RNA-sequencing study to analyze aggressive PCa specimens and matched non-cancer adjacent prostate tissue for insights as to the role of the microenvironment and potential PCa-stroma crosstalk.
Results: Results of our PCa cell line work indicate that a subpopulation of stem-cell like cancer cells produce IL6 and that IL6 acts in autocrine fashion to maintain that subpopulation. For the African American MDA-PCa2b cell line, IL6 expression was not detected. However, treatment of these cells with IL6 induced cancer stem cell-like prostasphere formation and growth. Results of our high-throughput gene expression analysis suggest that specifically for AAM, cancer cells are the source of pro-inflammatory cytokines in less aggressive cancer, but for aggressive prostate cancer pro-inflammatory cytokines originate from the non-cancer, prostate microenvironment.
Conclusion: our mechanism studies in PCa-derived cell lines and high-throughput functional genomic analyses of human specimens converge to improve understanding of the molecular biology unique to aggressive PCa in AAM. Continued research and development is warranted to show how this knowledge could be used to improve clinical decision-making and patient outcomes.
Citation Format: Aliccia B. Bollig-Fischer, Bin Bao, Christophe Legendre, Greg Dyson, Wael Sakr, John Carpten, Isaac Powell. The Role of Pro-Inflammatory Cytokines in Prostate Cancer in African American Men. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B34.
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