CHARACTERIZATION OF AN ESTABLISHED HUMAN, MALIGNANT, GLIOBLASTOMA CELL-LINE (GBM) AND ITS RESPONSE TO CONVENTIONAL DRUGS

A cell line, GBM, was established from a human malignant glioblastoma and was characterized with particular reference to its response to con ventional drugs. The GBM cell line exhibited a 73 +/- 7 h doubling tim e in monolayer cultures. Expression of glial fibrillary acidic and S-1 00 proteins was observed. Karyotype analysis of GBM cells at early pas sages revealed the presence of two near-triploid clones (A and B) with multiple chromosome rearrangements: a 100% frequency for clone B was observed in the established cell line. GBM cells had tumorigenic prope rties, since the s.c. injection of cultured cells into nude mice gave rise to slowly growing tumors. The morphology of GBM cells was retaine d during in vitro and in vivo passages, as judged by light microscopy. GBM cells were relatively resistant to most conventional drugs; among the tested drugs, only taxol exhibited a marked cytotoxic effect comp arable to that found in cells of a different tumor type. GBM cells wer e found positive for the epidermal growth factor receptor, HER2-neu an d P-glycoprotein by flow cytometry of cells labelled with monoclonal a ntibodies. In spite of the expression of relatively high gamma-glutamy ltransferase activity, the intracellular glutathione level was compara ble to that of other chemosensitive tumor cells. This glioblastoma cel l line is a suitable model for the identification and preclinical stud ies of new agents and provides an additional system to explore the mol ecular basis of the intrinsic drug resistance of glioblastoma.