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.
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Authors | Xu Zhang, Wenrong Xu, Hui Qian, Wei Zhu, Ruiwen Zhang |
Journal | Journal of cellular and molecular medicine
(J Cell Mol Med)
Vol. 15
Issue 2
Pg. 433-44
(Feb 2011)
ISSN: 1582-4934 [Electronic] England |
PMID | 19799647
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. |
Chemical References |
- NF-kappa B
- Recombinant Fusion Proteins
- tumstatin45-132-TNF
- Proto-Oncogene Proteins c-akt
- Extracellular Signal-Regulated MAP Kinases
- JNK Mitogen-Activated Protein Kinases
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Topics |
- Animals
- Apoptosis
- Cell Line, Tumor
- Cell Proliferation
- Coculture Techniques
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- Genetic Therapy
- Humans
- JNK Mitogen-Activated Protein Kinases
(metabolism)
- Lentivirus
(enzymology)
- Male
- Mesenchymal Stem Cells
(metabolism)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- NF-kappa B
(metabolism)
- Prostatic Neoplasms
(blood supply, metabolism, therapy)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Rats
- Recombinant Fusion Proteins
(genetics, metabolism)
- Transduction, Genetic
- Xenograft Model Antitumor Assays
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