Mesenchymal stem cells modified to express lentivirus TNF-α Tumstatin 45-132 inhibit the growth of prostate cancer

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Abstract

Mesenchymal stem cells (MSCs) are a potential novel delivery system for cell-based gene therapies. Although tumour necrosis factor (TNF)-α has been shown to have antitumour activity, its use in therapy is limited by its systemic toxicity. For the present study, we designed lentivirus-mediated signal peptide TNF-α-Tumstatin 45-132-expressing mesenchymal stem cells (SPTT-MSCs) as a novel anti-cancer approach. We evaluated the effects of this approach on human prostate cancer cells (PC3 and LNCaP) by co-culturing them with either SPTT-MSCs or supernatants from their culture medium in vitro. The antitumour effects and possible mechanisms of action of SPTT-MSCs were then determined in PC3 cells in vivo. The results showed that efficient TNF-α-Tumstatin 45-132-expressing MSCs had been established, and demonstrated that SPTT-MSCs inhibited the proliferation of and induced apoptosis in prostate cancer cells and xenograft tumours. As would be expected, given the properties of the individual proteins, the TNF-α-Tumstatin 45-132 fusion exerted potent cytotoxic effects on human prostate cancer cells and tumours via the death receptor-dependent apoptotic pathway and via antiangiogenic effects. Our findings suggest that SPTT-MSCs have significant activity against prostate cancer cells, and that they may represent a promising new therapy for prostate cancer. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

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Zhang, X., Xu, W., Qian, H., Zhu, W., & Zhang, R. (2011). Mesenchymal stem cells modified to express lentivirus TNF-α Tumstatin 45-132 inhibit the growth of prostate cancer. Journal of Cellular and Molecular Medicine, 15(2), 433–444. https://doi.org/10.1111/j.1582-4934.2009.00920.x

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