Estrogen receptor α in cancer associated fibroblasts suppresses prostate cancer invasion via reducing CCL5, IL6 and macrophage infiltration in the tumor microenvironment. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Yeh, Chiuan-Ren; Slavin, Spencer; Da, Jun; Hsu, Iawen; Luo, Jie; Xiao, Guang-Qian; Ding, Jie; Chou, Fu-Ju; Yeh, Shuyuan
• Is Part Of: Molecular cancer. Volume 15:Issue 1(2016)
• Page Start: 1
• Page End: 14
• Publication Date: 2016-12
• Subjects: CAF -- ERα -- CCL5 -- IL6 -- Tumor associated macrophages -- Prostate cancer; Cancer -- Molecular aspects -- Periodicals; 616.994
• DOI: 10.1186/s12943-015-0488-9
• Languages: English
• ISSNs: 1476-4598

Abstract

Abstract Background 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 Migration and invasion assays demonstrated the presence of high levels of ERα in CAF cells (CAF.ERα(+)) suppressed PCa invasionvia influencing the infiltration of tumor associated macrophages. ERα decreased CAF CCL5 secretionvia suppressing the CCL5 promoter activity was examined by luciferase assay. ERα decreased CCL5 and IL-6 expression in conditioned media that was collected from CAF cell only or CAF cell co-cultured with macrophages as measured by ELISA assay. Results Both in vitro and in vivo studies demonstrated CAF.ERα(+) led to a reduced macrophage migration toward PCavia inhibiting CAF cells secreted chemokine CCL5. 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. Conclusion Our data suggest that CAF ERα could be applied as a prognostic marker to predict cancer progression, 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.