Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis.
Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis.
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DOI：
10.1016/j.bbrc.2014.03.080
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发表时间：
2014-04
影响因子：
3.1
通讯作者：
K. Takahara;Masaaki Ii;T. Inamoto;K. Komura;N. Ibuki;K. Minami;H. Uehara;H. Hirano;H. Nomi;S. Kiyama;M. Asahi;H. Azuma
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文献类型：
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作者：
K. Takahara;Masaaki Ii;T. Inamoto;K. Komura;N. Ibuki;K. Minami;H. Uehara;H. Hirano;H. Nomi;S. Kiyama;M. Asahi;H. Azuma
间充质干细胞(MSCs)在再生医学领域引起了极大的兴趣。脂肪来源的基质细胞(AdSCs)具有广泛的增殖潜能，可以进行多向分化，具有与骨髓来源的MSCs相似的特性。然而，由于AdSCs对肿瘤生长的影响尚未得到充分的研究，我们评估了AdSCs对前列腺癌(Pca)细胞增殖的影响程度。人AdSCs对雄激素反应性(LNCaP)和雄激素非反应性(PC3)人PCa细胞的增殖有抑制作用，而正常人真皮成纤维细胞(NHDF)则无此作用，并在一定程度上促进了PCa细胞的增殖。此外，AdSCs还可诱导LNCaP细胞和PC3细胞的凋亡，激活caspase3/7信号通路。基因芯片分析表明，ADSC诱导LNCaP和PC3细胞的凋亡与转化生长因子-β信号通路有关。与我们的体外观察一致，AdSCs的局部移植延缓了来自免疫缺陷小鼠的LNCaP和PC3异种移植瘤的生长。这是第一个直接证明脂肪干细胞诱导PCa细胞凋亡可能通过转化生长因子-β信号通路发生的临床前研究，与雄激素反应无关。由于自体AdSCs可以很容易地从脂肪组织中分离出来，而不存在任何伦理问题，我们建议用这些细胞治疗PCa患者可能是一种新的方法。
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.