Abstract 4004: Rapamycin selectively targets obesity-polarized macrophages in the prostate tumor microenvironment

Abstract

Background: Obesity is associated with prostate cancer progression and mortality. Previous studies in our laboratory suggest that obesity drives prostate cancer progression in part by increasing macrophage recruitment and by polarizing macrophages in the tumor microenvironment into a tumor promoting M2/TAM phenotype. Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has been used for several decades in transplant patients, and in the last several years has been shown to be an effective disease suppressor in certain cancer types. Intriguingly, mTOR has been shown to be especially important for M2 polarization and stabilization. Hypothesis: Based upon published data and our preliminary studies, we hypothesize that rapamycin will selectively target obesity-polarized macrophages and will provide a survival benefit to the obese prostate cancer patient. Methods: To address this hypothesis, we used our in vitro model of obesity-induced macrophage polarization that includes two different prostate cancer cell lines, macrophages, and sera from obese and non-obese men. qPCR was used to measure expression levels of markers associated with an M2/TAM phenotype. MTT assays were conducted to measure cell viability, and flow cytometry and Western blot analyses were used to determine cell cycle status and apoptosis. Results: Obese conditions increased expression of M2/TAM markers in macrophages and rapamycin selectively decreased viability of obesity-activated M2/TAMs compared to M1 macrophages. Conclusions: Our in vitro study suggests that obesity promotes a tumor-associated phenotype in macrophages and that the mTOR pathway is involved in the survival of M2/TAM macrophages. This study offers a novel mechanistic approach to treat obese patients with prostate cancer. Citation Format: Gloria C. Galván, Tommy Pham, Brittany Harlow, Christian Johnson, Riddhi Patodia, Duan Quach, Michael A. Liss, Linda A. deGraffenried. Rapamycin selectively targets obesity-polarized macrophages in the prostate tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4004. doi:10.1158/1538-7445.AM2017-4004