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Glioma gene therapy with soluble transforming growth factor-beta receptors II and III
- Source :
- International journal of oncology. 33(4)
- Publication Year :
- 2008
-
Abstract
- Transforming growth factor-beta (TGF-beta) is abundantly expressed in malignant gliomas and is crucial for the tumor micromilieu. TGF-beta not only enhances migration and invasion of glioma cells but also inhibits an effective anti-glioma immune response. TGF-beta mediates its biologic effects through interactions with TGF-beta receptors (TbetaR)-I to -III. Binding of TGF-beta leads to the activation of an intracellular signaling cascade and subsequent phosphorylation of Sma and MAD-related proteins (SMAD). Soluble TGF-beta receptors (TbetaRs) abrogate the TGF-beta effect by competing for the binding of the ligand to its receptor. Here we used adenoviral gene transfer to express TbetaR-IIs and -IIIs in human glioma cell lines. TbetaR-IIs reduced SMAD2 phosphorylation and TGF-beta-dependent reporter activity. Furthermore, it enhanced glioma cell lysis by natural killer cells. TbetaR-IIIs alone were inactive in these assays, but enhanced the effects of TbetaR-IIs. Transduction of LN-308 cells with TbetaRs markedly delayed growth of intracerebral xenografts in nude mice in vivo. These data commend TbetaRs for possible experimental therapy of gliomas.
- Subjects :
- Brain Neoplasms
Cell Survival
Receptor, Transforming Growth Factor-beta Type II
Mice, Nude
Genetic Therapy
Glioma
Protein Serine-Threonine Kinases
Killer Cells, Natural
Mice
Transforming Growth Factor beta
Cell Line, Tumor
Animals
Humans
Proteoglycans
Receptors, Transforming Growth Factor beta
Neoplasm Transplantation
Protein Binding
Subjects
Details
- ISSN :
- 10196439
- Volume :
- 33
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- International journal of oncology
- Accession number :
- edsair.pmid..........f406f129f918913ec893d1da8f918a03