title: Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis.
abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.
authors.affiliation: Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takahara
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka, Japan. Electronic address: masaii@art.osaka-med.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ii
authors.affiliation: Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Inamoto
authors.affiliation: Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Komura
authors.affiliation: Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Naokazu
authors.initials: N
authors.lastname: Ibuki
authors.affiliation: Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Minami
authors.affiliation: Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uehara
authors.affiliation: Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Hirano
authors.affiliation: Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Hayahito
authors.initials: H
authors.lastname: Nomi
authors.affiliation: Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kiyama
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Asahi
authors.affiliation: 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*; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D051379:Mice; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016212:Transforming Growth Factor beta
keywords: AdSCs; Apoptosis; PCa; Prostate cancer; Stem cell