MP87-13 ESTROGEN RECEPTOR α IN CANCER ASSOCIATED FIBROBLASTS SUPPRESSES PROSTATE CANCER INVASION VIA REDUCING CCL5, IL6 AND MACROPHAGE INFILTRATION IN THE TUMOR MICROENVIRONMENT.

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III1 Apr 2017MP87-13 ESTROGEN RECEPTOR α IN CANCER ASSOCIATED FIBROBLASTS SUPPRESSES PROSTATE CANCER INVASION VIA REDUCING CCL5, IL6 AND MACROPHAGE INFILTRATION IN THE TUMOR MICROENVIRONMENT. Yang Yang, Chiuan-Ren Yeh, Spencer Slavin, Jie Luo, Fu-Ju Chou, Keliang Wang, Matthew Truong, Chawnshang Chang, Edward M. Messing, and Shuyuan Yeh Yang YangYang Yang More articles by this author , Chiuan-Ren YehChiuan-Ren Yeh More articles by this author , Spencer SlavinSpencer Slavin More articles by this author , Jie LuoJie Luo More articles by this author , Fu-Ju ChouFu-Ju Chou More articles by this author , Keliang WangKeliang Wang More articles by this author , Matthew TruongMatthew Truong More articles by this author , Chawnshang ChangChawnshang Chang More articles by this author , Edward M. MessingEdward M. Messing More articles by this author , and Shuyuan YehShuyuan Yeh More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2717AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cancer associated fibroblasts (CAF) play important roles in tumor growth that involves inflammation and epithelial cell differentiation. Early studies suggested that estrogen receptor alpha (ERα) was expressed in stromal cells in normal prostates and prostate cancer (PCa), but the detailed functions of stromal ERα in the PCa remain to be further elucidated. METHODS In vitro study, we applied migration and invasion assays to demonstrated whether the levels of ERα in CAF cells (CAF.ERα(+)) could suppress PCa invasion via influencing the infiltration of tumor associated macrophages. Q-PCR, Elisa assay and luciferase assay were used to detect which cytokines may mediate the CAF.ERα(+) suppressed macrophage infiltration and PCa invasion. In vivo study, nude mice were orthotopically implanted with CAF.ERα(+) or CAF.ERα(-) mixed with CWR22Rv1 cells. Then, IHC was used to verify the data in vitro study. We further examined the ERα, CD206, CCL5 and IL6 expressions in 14 human PCa tissue specimens by IHC staining. RESULTS Both in vitro and in vivo mouse PCa model studies demonstrated CAF.ERα(+) led to a reduced macrophage migration toward PCa via inhibiting CAF cells secreted chemokine CCL5 (Figure1 and 3). This CAF.ERα(+) suppressed macrophage infiltration affected the neighboring PCa cells invasion and the reduced invasiveness of PCa cells are at least partly due to reduced IL6 expression in the macrophages and CAF. (Figure 2). In human PCa tissues, our results showed a positive correlation between ERα, M2 macrophages, CCL5 and IL-6. In high stromal ERα expression samples, the expression levels of CD206 (M2 macrophage marker), CCL5 and IL6 were higher than in samples with low stromal ERα expression (Figure 4). CONCLUSIONS Our data suggest that CAF ERα could be applied as a prognostic marker to predict the recurrence-free survival, and targeting CCL5 and IL6 may be applied as an alternative therapeutic approach to reduce M2 type macrophages and PCa invasion in PCa patients with low or little ERα expression in CAF cells. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1170-e1171 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Yang Yang More articles by this author Chiuan-Ren Yeh More articles by this author Spencer Slavin More articles by this author Jie Luo More articles by this author Fu-Ju Chou More articles by this author Keliang Wang More articles by this author Matthew Truong More articles by this author Chawnshang Chang More articles by this author Edward M. Messing More articles by this author Shuyuan Yeh More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...