Tumor necrosis factor-alpha gene transfer augments anti-Fas antibody-mediated apoptosis in human glioma cells.
To effectively induce apoptosis in human glioma cells, we tried to transfer the tumor necrosis factor (TNF)-alpha gene into glioma cells to produce TNF-alpha locally in these cells. The stable transfectants of three glioma cells (U251-SP, U251-MG, and T98G) were resistant to exogenous TNF-alpha, but their cell surface expression of the Fas antigen was dramatically enhanced by about 10 to 100-fold as compared with untransfected glioma cells exposed to exogenous TNF-alpha. The Fas antigen is a transmembrane cytokine receptor protein of the nerve growth factor/TNF receptor superfamily. Although the untransfected glioma cells tested were resistant to anti-Fas antibody-mediated apoptosis, the TNF-alpha gene-transfected glioma cells exhibited high susceptibility to anti-Fas antibody-mediated apoptosis. Thus, TNF-alpha gene transfer combined with anti-Fas antibodies may be useful for the treatment of malignant glioma.
Mizuno
M
M
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
Yoshida
J
J
D000906:Antibodies / Q000627:therapeutic use*; D017209:Apoptosis; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018014:Gene Transfer Techniques; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D019014:fas Receptor / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor