Abstract
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.
Highlights
mesenchymal stem cells (MSCs) originating from the mesodermal germ layer are a subset of nonhematopoietic stem cells existed in bone marrow[5,6]
The results suggested that MSCs that existed in Prostate cancer (PCa) specimens might promote the development of PCa which lead to a poor prognosis of PCa patients
Solid tumors are composed of tumor cells and supportive non-tumor components known as tumor stroma
Summary
MSCs originating from the mesodermal germ layer are a subset of nonhematopoietic stem cells existed in bone marrow[5,6]. MSCs have a tropism for tumors[13] and several studies have reported contradictory results about the effect of MSCs on tumor growth. Djouad et al.[15] showed that MSCs had displayed side effects related to systemic immunosupression favoring tumor growth in vivo. The stroma tissue is an important part of tumor and MSCs is the progenitor cells of stromal cells. We suppose that MSCs may play a key role in inducing androgen resistance in human prostate cancer cells. We used LNCaP prostate cancer cell line to investigate the effect of MSCs on the transformation of androgen-dependent human PCa cells into androgen-independent manner and the potential mechanism
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