Effects of type beta transforming growth factor in combination with retinoic acid or tumor necrosis factor on proliferation of a human glioblastoma cell line and clonogenic cells from freshly resected human brain tumors.
Type beta transforming growth factor (beta-TGF) is a potent regulator of cell growth and differentiation. The human glioblastoma cell line, T-MGI, was growth inhibited by beta-TGF under anchorage independent conditions. The antiproliferative effect of beta-TGF was potentiated to nearly total arrest by low doses of retinoic acid (RA) or tumor necrosis factor (TNF), while epidermal growth factor, platelet-derived growth factor, interleukin-2, and gamma interferon did not have this potentiating effect. The potentiation of the beta-TGF effect by RA and TNF could not be explained by modulation of the epidermal growth factor receptor, the beta-TGF receptor, or the TNF receptor. beta-TGF alone and in combination with RA or TNF were further tested on primary cultures from freshly resected human glioma biopsies (n = 13). There was great individual variation in sensitivity to beta-TGF, RA, or TNF. The astrocytoma and oligodendroglioma cells were inhibited to various degrees by beta-TGF or TNF, while most of the glioblastomas were not sensitive to these agents. Most of the biopsies were stimulated by RA. RA or TNF did not potentiate the growth inhibitory effect of beta-TGF on biopsy cells. We therefore think it unlikely that beta-TGF in combination with RA or TNF will be effective agents in the treatment of gliomas.
Helseth
E
E
Institute of Cancer Research, University of Trondheim, Norway.
Unsgaard
G
G
Dalen
A
A
Vik
R
R
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002460:Cell Line; D002999:Clone Cells / Q000187:drug effects / Q000473:pathology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D066246:ErbB Receptors / Q000032:analysis / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy / Q000473:pathology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007457:Iodine Radioisotopes; D010455:Peptides / Q000494:pharmacology; D012685:Sepharose; D015291:Transforming Growth Factors; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D007457:Iodine Radioisotopes; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D015291:Transforming Growth Factors; D012685:Sepharose; D066246:ErbB Receptors