The role of mesenchymal stem cells in promoting the transformation of androgen-dependent human prostate cancer cells into androgen-independent manner.
The role of mesenchymal stem cells in promoting the transformation of androgen-dependent human prostate cancer cells into androgen-independent manner.
复制标题
DOI：
10.1038/srep16993
复制
发表时间：
2016-01-20
影响因子：
4.6
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Cheng J;Yang K;Zhang Q;Yu Y;Meng Q;Mo N;Zhou Y;Yi X;Ma C;Lei A;Liu Y
间充质干细胞（Mesenchymal stem cells，MSCs）在前列腺癌（prostate cancer，PCa）的发生发展中起重要作用。然而，MSC在雄激素依赖性人前列腺癌细胞转化为雄激素非依赖性方式中的作用知之甚少。本研究旨在探讨骨髓间充质干细胞促进前列腺癌细胞由雄激素依赖型向雄激素非依赖型转化的机制。首先，我们在体内和体外证明了MSC可以影响雄激素依赖性人前列腺癌细胞向雄激素非依赖性细胞的转化。TGF-β在MSCs中有大量表达。TGF-β阻断可明显抑制MSCs对PCa细胞的促增殖作用。此外，雄激素还可以抑制MSCs中TGF-β的表达。此外，我们发现，无论是过度表达SSEA-4或SSEA-4阳性的MSC在PCa组织中的数量与较短的无癌生存期（CFSI）和较差的总生存期（OS）。结果提示，雄激素阻断治疗PCa可诱导MSC表达TGF-β，使雄激素依赖型PCa细胞向雄激素非依赖型转化。
Mesenchymal stem cells (MSCs) play an important role in the development of human prostate cancer (PCa). However, the role of MSCs in the transformation of androgen-dependent human PCa cells into androgen-independent manner has been poorly understood. In this study, we investigated the underlying mechanism of MSCs in promoting PCa cells from androgen-dependent into androgen-independent manner. Firstly, we demonstrated that MSCs could affect the transformation of androgen-dependent human PCa cells into androgen-independent manner in vivo and in vitro. Then we found a substantial expression of TGF-β in MSCs. TGF-β blockade could significantly inhibit the promotive function of MSCs in PCa cells. Besides that, we also demonstrated androgen might inhibit the expression of TGF-β in MSCs. Furthermore, we found that either overexpression of SSEA-4 or the number of SSEA-4 positive MSCs in PCa tissues was associated with a shorter cancer-free survival interval (CFSI) and a worse overall survival (OS). Our results suggest that androgen blockade treatment in clinical PCa therapy may elicit the expression of TGF-β in MSCs, which will result in the transformation of androgen-dependent human PCa cells into androgen-independent manner.