Glioma gene therapy with soluble transforming growth factor-β receptors II and III

  • Authors: Ulrike Naumann, Philipp Maass, Anne-Kathrin Gleske, Steffen Aulwurm, Michael Weller, Guenter Eisele
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  • Published online on: Wednesday, October 1, 2008
  • Pages: 759-765
  • DOI: 10.3892/ijo_00000062

Abstract

Transforming growth factor-β (TGF-β) is abundantly expressed in malignant gliomas and is crucial for the tumor micromilieu. TGF-β not only enhances migration and invasion of glioma cells but also inhibits an effective anti-glioma immune response. TGF-β mediates its biologic effects through interactions with TGF-β receptors (TβR)-I to -III. Binding of TGF-β leads to the activation of an intracellular signaling cascade and subsequent phosphorylation of Sma and MAD-related proteins (SMAD). Soluble TGF-β receptors (TβRs) abrogate the TGF-β effect by competing for the binding of the ligand to its receptor. Here we used adenoviral gene transfer to express TβR-IIs and -IIIs in human glioma cell lines. TβR-IIs reduced SMAD2 phosphorylation and TGF-β-dependent reporter activity. Furthermore, it enhanced glioma cell lysis by natural killer cells. TβR-IIIs alone were inactive in these assays, but enhanced the effects of TβR-IIs. Transduction of LN-308 cells with TβRs markedly delayed growth of intracerebral xenografts in nude mice in vivo. These data commend TβRs for possible experimental therapy of gliomas.
Journal Cover

October 2008
Volume 33 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Naumann, U., Maass, P., Gleske, A., Aulwurm, S., Weller, M., & Eisele, G. (2008). Glioma gene therapy with soluble transforming growth factor-β receptors II and III. International Journal of Oncology, 33(4), 759-765.
MLA
Naumann, Maass, Gleske, Aulwurm, Weller, and Guenter Eisele. "Glioma gene therapy with soluble transforming growth factor-β receptors II and III." International Journal of Oncology International Journal of Oncology 33.4 (2008): 759-765.
Chicago
Naumann, Maass, Gleske, Aulwurm, Weller, and Guenter Eisele. "Glioma gene therapy with soluble transforming growth factor-β receptors II and III." International Journal of Oncology International Journal of Oncology 33 no. 4 (2008): 759-765.