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

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.
AuthorsXu Zhang, Wenrong Xu, Hui Qian, Wei Zhu, Ruiwen Zhang
JournalJournal of cellular and molecular medicine (J Cell Mol Med) Vol. 15 Issue 2 Pg. 433-44 (Feb 2011) ISSN: 1582-4934 [Electronic] England
PMID19799647 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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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