Gamma-glutamyl transferase expression in higher-grade astrocytic glioma

Increased expression of gamma -glutamyltransferase (GGT) has been detected in a range of human malignancies and is thought to be involved in neoplasti c proliferation and treatment resistance. Since GGT expression and its role in malignant glioma biology remain largely unknown, we investigated this p henomenon by immunostaining 26 higher-grade human astrocytic gliomas (WHO g rades III and IV) with a monoclonal anti-GGT-antibody (138H11). Further, hu man pancreatic GGT cDNA was used for liposome-mediated transfection of 9L g liosarcoma cells. GGT-expressing and control 9L cells were cultured in medi a containing different amounts of essential amino acids and/or cytotoxic ag ents. Cell viability was evaluated by microplate MTT assay. Immunohistochem ical staining of tumor specimens demonstrated that GGT expression is a freq uent feature of higher-grade human astrocytic gliomas, but not of normal br ain tissue. Human tumors were strongly GGT-positive in 6 of 7 cases of grad e III astrocytoma, and in 12 of 19 grade IV astrocytoma (glioblastoma multi forme, GBM) cases. In the cell culture model, 9L-GGT cells had a growth adv antage over control cells in cysteine-deficient medium, but not in standard or glutamine-free medium. No significant difference in numbers of viable c ells of either clone was found in media containing the alkylating drug BCNU (5-200 mug/ml). In conclusion, GGT is expressed in a high percentage of hu man WHO grade III astrocytomas and GBM, but not in normal brain tissue. Thi s molecule seems to give neoplastic cells a moderate growth advantage under in vivo conditions.