Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

•AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells.•AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway.•High expression of the TGF-β1 gene in AdSCs. Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerat...

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Veröffentlicht in:Biochemical and biophysical research communications 2014-04, Vol.446 (4), p.1102-1107
Hauptverfasser: Takahara, Kiyoshi, Ii, Masaaki, Inamoto, Teruo, Komura, Kazumasa, Ibuki, Naokazu, Minami, Koichiro, Uehara, Hirofumi, Hirano, Hajime, Nomi, Hayahito, Kiyama, Satoshi, Asahi, Michio, Azuma, Haruhito
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container_end_page 1107
container_issue 4
container_start_page 1102
container_title Biochemical and biophysical research communications
container_volume 446
creator Takahara, Kiyoshi
Ii, Masaaki
Inamoto, Teruo
Komura, Kazumasa
Ibuki, Naokazu
Minami, Koichiro
Uehara, Hirofumi
Hirano, Hajime
Nomi, Hayahito
Kiyama, Satoshi
Asahi, Michio
Azuma, Haruhito
description •AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells.•AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway.•High expression of the TGF-β1 gene in AdSCs. 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.
doi_str_mv 10.1016/j.bbrc.2014.03.080
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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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24680678</pmid><doi>10.1016/j.bbrc.2014.03.080</doi><tpages>6</tpages></addata></record>
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ispartof Biochemical and biophysical research communications, 2014-04, Vol.446 (4), p.1102-1107
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source MEDLINE; Elsevier ScienceDirect Journals
subjects 60 APPLIED LIFE SCIENCES
ADIPOSE TISSUE
Adipose Tissue - cytology
AdSCs
ANDROGENS
Animals
APOPTOSIS
BONE MARROW
Cell Line, Tumor
CELL PROLIFERATION
DRUGS
FIBROBLASTS
GENES
HUMAN POPULATIONS
Humans
IN VITRO
Male
MICE
NEOPLASMS
PATIENTS
PCa
PROSTATE
Prostate - metabolism
Prostate - pathology
Prostate cancer
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Prostatic Neoplasms - therapy
Signal Transduction
Stem cell
STEM CELLS
Stromal Cells - cytology
Stromal Cells - metabolism
Stromal Cells - transplantation
THERAPY
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - metabolism
Up-Regulation
title Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis
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