Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Ständer, M. et al.

Decorin gene transfer- mediated suppression of TGF-beta synthesis abrogates experimental malignant glioma growth in vivo.

Cytokines such as transforming growth factor-beta ( TGF-beta) are thought to mediate escape from immune surveillance in human malignant glioma. Here, we report that ectopic expression of the small TGF-beta-binding proteoglycan, decorin, inhibits not only TGF-beta bioactivity but also TGF-beta 1 and TGF-beta 2 mRNA transcription and TGF-beta protein synthesis by human LN-18, LN-229, T98G and rat C6 glioma cells in vitro. Ectopic expression of decorin in C6 rat glioma cells results in strong inhibition of tumor formation in vivo. Decorin-expressing C6 gliomas grow initially but regress to very small residual tumors at 12 weeks after implantation whereas all control animals die or have to be killed within 4 weeks. Decorin-expressing tumors show a four-fold increase of infiltration by activated T cells and a 1.6-fold increase in total B and T cells. Chronic steroid-mediated immunosuppression abrogates the inhibitory effects of decorin gene transfer. We conclude that decorin- induced inhibition of TGF-beta release by glioma cells significantly enhances antiglioma immune responses in vivo. Clinical evaluation of decorin gene therapy for human malignant gliomas may be warranted.[1]

References

Decorin gene transfer-mediated suppression of TGF-beta synthesis abrogates experimental malignant glioma growth in vivo. Ständer, M., Naumann, U., Dumitrescu, L., Heneka, M., Löschmann, P., Gulbins, E., Dichgans, J., Weller, M. Gene Ther. (1998) [Pubmed]

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