Abstract 1156: Skeletal muscle progenitor cell-derived exosomes have therapeutic potential in inhibition of prostate cancer cell proliferation

Abstract

Abstract Adult stem cells have been used as regenerative medicine for treating human diseases through gene therapy approach. These stem cells secrete cytokines, growth factors and extracellular vesicles including exosomes, which may induce antitumor activities. We have demonstrated that muscle progenitor cells (MPCs) from adult (murine and human) skeletal muscle have a high regenerative potential to repair bone, skeletal muscle, and cartilage. However, to date, the potential therapeutic use of MPCs in cancers has not yet been investigated. The objectives of this study were to identify and examine the roles of secreted factors including exosomes from MPCs on the proliferation/survival, motility/migration and invasive potential of prostate cancer (PCa) cells. Here we showed that co-culture of PCa cell lines, PC3 and C42B, with MPCs in trans-well inserts strongly suppressed PCa cell proliferation and survival by activating CDK inhibitors (p16 and p27) and apoptotic BBC3 and NOXA genes. Mass spectrometry analysis of factors secreted by MPCs identified several proteins with known anti-proliferative functions, including IGFBP6/7, pigment epithelium-derived factor (PEDF), HPCAL1, NO, and SPARC. Conditioned media (CM) from MPCs significantly increased docetaxel-induced cytotoxicity of PCa cells by suppressing the expression of key genes including AR, MLL, FOXA1, TWF1, and TGIF. Next, we isolated exosomes from cultured mouse and human MPCs through step-wise ultracentrifugation methods and tested their effect in the proliferation of cancer cells. We observed that treatment of PCa cells with MPC-derived exosomes inhibited cell proliferation as assayed with MTT and down-regulated the expression of AR and its target NKX3.1 genes. We also observed that the migration ability of ovarian cancer cells (OVAC5) and pancreatic cancer (Panc1), was markedly reduced following MPC-derived exosome treatments compared to untreated cells. Taken together, our data suggest that MPCs can suppress the proliferation and survival of cancer cells through secreted factors including exosomes. Thus, adult stem cell-based therapy along with existing therapies may be a promising strategy in treating various solid cancers as well as regenerating cancer-induced bone and muscle tissue lesions. Citation Format: Krishna M. Sinha, Rozita Yarmand, Nermin Kahraman, Fahriye Duzagac, Gabriel Lopez, Bulent Ozpolat, Johnny Huard. Skeletal muscle progenitor cell-derived exosomes have therapeutic potential in inhibition of prostate cancer cell proliferation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1156.