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MicroRNA-145 mediates the inhibitory effect of adipose-derived stem cells on androgenindependent prostate cancer Eur Urol Suppl 2016;15(3);e245
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Takahara K., Inamoto T., Ibuki N., Uchimoto T., Saito K., Takai T., Tanda N., Hirano H., Nomi H., Kiyama S., Azuma H. Osaka Medical College, Dept. of Urology, Takatsuki, Japan INTRODUCTION & OBJECTIVES: Adipose-derived Stem Cells (AdSCs), known as one of the Mesenchymal Stem Cells (MSCs), have an important role for carcinogenesis, however, the effect of AdSCs on tumor growth has not been studied sufficiently. We have previously reported that AdSCs directly inhibited the proliferation of two different types of Prostate Cancer (PCa) cells, androgen-responsive (LNCaP) and androgen–nonresponsive (PC3) cells, inducing apoptosis both in vitro and in vivo. MATERIAL & METHODS: To elucidate further mechanism of AdSCs-induced inhibitory effect on PCa activity, we carried out in vitro and in vivo studies using a luciferase-expressing metastatic PCa cell line which was stably transfected with firefly luciferase gene (luc2), PC3Mluc2, originated from PC3, with human AdSCs under direct co-culture and indirect separate culture conditions. We also performed Exosome microRNAs (miRNAs) array analysis to explore a mechanistic insight into the effect of AdSCs on PCa cell proliferation/apoptosis. RESULTS: Both in vitro and in vivo co-culture experiments revealed the anti-proliferative effect of AdSCs inducing apoptosis in PC3M-luc2 cells. Inhibition of miR-145, whose expression was much higher in AdSCs than in NHDF on Exosome miRNAs array analysis, demonstrated that AdSCs-derived miR-145 played a pivotal role for the suppression of PCa progression. CONCLUSIONS: This study provides the preclinical data to indicate that AdSCs inhibit androgen-independent PCa growth both in vitro and in vivo inducing apoptosis by miR-145 secretion, suggesting that this might be a promising novel therapeutic approach for patients with PCa.