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

Kiyoshi Takahara, Masaaki Ii, Teruo Inamoto, Kazumasa Komura, Naokazu Ibuki, Koichiro Minami, Hirofumi Uehara, Hajime Hirano, Hayahito Nomi, Satoshi Kiyama, Michio Asahi, Haruhito Azuma

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1102-1107
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume446
Issue number4
DOIs
Publication statusPublished - 18-04-2014
Externally publishedYes

Fingerprint

Cell proliferation
Stromal Cells
Androgens
Prostatic Neoplasms
Cell Proliferation
Apoptosis
Stem cells
Tumors
Fibroblasts
Microarrays
Heterografts
Bone
Complementary DNA
Cells
Tissue
Mesenchymal Stromal Cells
Regenerative Medicine
Microarray Analysis
Growth
Cell- and Tissue-Based Therapy

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Takahara, Kiyoshi ; Ii, Masaaki ; Inamoto, Teruo ; Komura, Kazumasa ; Ibuki, Naokazu ; Minami, Koichiro ; Uehara, Hirofumi ; Hirano, Hajime ; Nomi, Hayahito ; Kiyama, Satoshi ; Asahi, Michio ; Azuma, Haruhito. / Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis. In: Biochemical and Biophysical Research Communications. 2014 ; Vol. 446, No. 4. pp. 1102-1107.
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Takahara, K, Ii, M, Inamoto, T, Komura, K, Ibuki, N, Minami, K, Uehara, H, Hirano, H, Nomi, H, Kiyama, S, Asahi, M & Azuma, H 2014, 'Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis', Biochemical and Biophysical Research Communications, vol. 446, no. 4, pp. 1102-1107. https://doi.org/10.1016/j.bbrc.2014.03.080

Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis. / Takahara, Kiyoshi; Ii, Masaaki; Inamoto, Teruo; Komura, Kazumasa; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Asahi, Michio; Azuma, Haruhito.

In: Biochemical and Biophysical Research Communications, Vol. 446, No. 4, 18.04.2014, p. 1102-1107.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

AU - Takahara, Kiyoshi

AU - Ii, Masaaki

AU - Inamoto, Teruo

AU - Komura, Kazumasa

AU - Ibuki, Naokazu

AU - Minami, Koichiro

AU - Uehara, Hirofumi

AU - Hirano, Hajime

AU - Nomi, Hayahito

AU - Kiyama, Satoshi

AU - Asahi, Michio

AU - Azuma, Haruhito

PY - 2014/4/18

Y1 - 2014/4/18

N2 - 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.

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