Abstract LB-268: Androgen signaling in cancer-associated fibroblasts contributes to progression of prostate cancer

Abstract

Abstract Interactions between epithelial and stromal cells are important in the development of prostate cancer (PCa). Cancer-associated fibroblasts (CAFs) have been to support tumor progression, metastasis, and differentiation. Androgen receptor (AR) and related pathways are known to support the growth and survival of prostate epithelial cancer cells, the roles of AR-dependent processes in cancerous stroma are less clear. We sought to investigate if AR-dependent pathways present in CAF cells influence the growth and tumorogencity of epithelial cancer cells in relation to androgen-deprivation therapy in prostate cancer. Murine CAFs were isolated from a well-described PTEN-dependent cancer mouse model. A co-culture system was developed based on multiple lines of murine CAFs grown along with human prostate cancer epithelial cells, and a murine-specific anti-sense oligonucleotide (ASO) against murine AR was used to specifically suppress AR expression in murine CAFs in this system. Using this co-culture system, we found that murine CAFs promoted cell proliferation and colony formation in several human prostate cancer cell lines. Further, these processes were decreased by suppression of AR-expression in CAFs. Expression of genes related to tumorogenicity in epithelial cells were investigated by real-time quantitative PCR. Markers associated with epithelial-mesenchymal transition (EMT) and stemness were increased in human prostate cancer cells grown with low-AR CAFs. Our data indicates that suppression of AR in CAFs results in down-regulation in the growth and tumorogenecity of prostate cancer cells through pathways related to EMT and “cell reprograming”. As such, development of therapies which inhibit the tumor-promoting pathways present in stromal cells may be one approach to improve the treatment of prostate cancer. Citation Format: Chun-Peng Liao, Leng-Ying Chen, Andrea Luethy, Youngsoo Kim, Robert MacLeod, Mitchell Gross. Androgen signaling in cancer-associated fibroblasts contributes to progression of prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-268.