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
  • View Affiliations

  • Published online on: October 1, 2008     https://doi.org/10.3892/ijo_00000062
  • Pages: 759-765
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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.

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October 2008
Volume 33 Issue 4

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

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Spandidos Publications style
Naumann U, Maass P, Gleske A, Aulwurm S, Weller M and Eisele G: Glioma gene therapy with soluble transforming growth factor-β receptors II and III. Int J Oncol 33: 759-765, 2008
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, 759-765. https://doi.org/10.3892/ijo_00000062
MLA
Naumann, U., Maass, P., Gleske, A., Aulwurm, S., Weller, M., Eisele, G."Glioma gene therapy with soluble transforming growth factor-β receptors II and III". International Journal of Oncology 33.4 (2008): 759-765.
Chicago
Naumann, U., Maass, P., Gleske, A., Aulwurm, S., Weller, M., Eisele, G."Glioma gene therapy with soluble transforming growth factor-β receptors II and III". International Journal of Oncology 33, no. 4 (2008): 759-765. https://doi.org/10.3892/ijo_00000062