title: microRNA-145 Mediates the Inhibitory Effect of Adipose Tissue-Derived Stromal Cells on Prostate Cancer.
abstract: Adipose-derived stromal cell (ASC), known as one of the mesenchymal stem cells (MSCs), is a promising tool for regenerative medicine; however, the effect of ASCs on tumor growth has not been studied sufficiently. We investigated the hypothesis that ASCs have an inhibitory effect on metastatic tumor progression. To evaluate the in vitro inhibitory effect of ASCs on metastatic prostate cancer (PCa), direct coculture and indirect separate culture experiments with PC3M-luc2 cells and human ASCs were performed, and ASCs were administered to PC3M-luc2 cell-derived tumor-bearing nude mice for in vivo experiment. We also performed exosome microRNA (miRNA) array analysis to explore a mechanistic insight into the effect of ASCs on PCa cell proliferation/apoptosis. Both in vitro and in vivo experiments exhibited the inhibitory effect of ASCs on PC3M-luc2 cell proliferation, inducing apoptosis and PCa growth, respectively. Among upregulated miRNAs in ASCs compared with fibroblasts, we focused on miR-145, which was known as a tumor suppressor. ASC-derived conditioned medium (CM) significantly inhibited PC3M-luc2 cell proliferation, inducing apoptosis, but the effect was canceled by miR-145 knockdown in ASCs. ASC miR-145 knockdown CM also reduced the expression of Caspase 3/7 with increased antiapoptotic protein, BclxL, expression in PC3M-luc2 cells. This study provides preclinical data that ASCs inhibit PCa growth, inducing PCa cell apoptosis with reduced activity of BclxL, at least in part, by miR-145, including exosomes released from ASCs, suggesting that ASC administration could be a novel and promising therapeutic strategy in patients with PCa.
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takahara
authors.affiliation: 2 Department of Pharmacology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .|3 Division of Research Animal Laboratory and Translational Medicine, Research and Development Center, Osaka Medical College , Osaka, Japan .
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ii
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Teruo
authors.initials: T
authors.lastname: Inamoto
authors.affiliation: 2 Department of Pharmacology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Naokazu
authors.initials: N
authors.lastname: Ibuki
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshikawa
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsujino
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Taizo
authors.initials: T
authors.lastname: Uchimoto
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Saito
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Takai
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Naoki
authors.initials: N
authors.lastname: Tanda
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Koichiro
authors.initials: K
authors.lastname: Minami
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uehara
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Komura
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Hajime
authors.initials: H
authors.lastname: Hirano
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Hayahito
authors.initials: H
authors.lastname: Nomi
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kiyama
authors.affiliation: 2 Department of Pharmacology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Michio
authors.initials: M
authors.lastname: Asahi
authors.affiliation: 1 Department of Urology, Faculty of Medicine, Osaka Medical College , Osaka, Japan .
authors.forename: Haruhito
authors.initials: H
authors.lastname: Azuma
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D055354:Exosomes / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D017154:Stromal Cells / Q000166:cytology; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D051020:bcl-X Protein