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

Gene Ther. 1998 Sep;5(9):1187-94. doi: 10.1038/


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • B-Lymphocytes / immunology
  • Blotting, Northern
  • Decorin
  • Dexamethasone / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix Proteins
  • Female
  • Gene Expression
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Glioma / immunology
  • Glioma / therapy*
  • Humans
  • Immunoblotting
  • Lymphocyte Activation
  • Neoplasm Transplantation
  • Proteoglycans / analysis
  • Proteoglycans / genetics*
  • Proteoglycans / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • T-Lymphocytes / immunology
  • Transforming Growth Factor beta / metabolism*
  • Tumor Cells, Cultured


  • Anti-Inflammatory Agents
  • DCN protein, human
  • Dcn protein, rat
  • Decorin
  • Extracellular Matrix Proteins
  • Proteoglycans
  • Transforming Growth Factor beta
  • Dexamethasone