SUPPRESSION OF THE MALIGNANT PHENOTYPE OF HUMAN GLIOMA-CELLS BY OVEREXPRESSION OF MANGANESE SUPEROXIDE-DISMUTASE

Manganese superoxide dismutase (MnSOD) has been previously shown to su ppress the malignant phenotype of human melanoma and breast cancer cel ls, To test the possible role of MnSOD in glioma malignancy, MnSOD was overexpressed in wild type human glioma U118 cells and subcloned U118 -9 cells by transfection of human MnSOD cDNA, The MnSOD-transfected ce ll lines demonstrated expression of exogenous (plasmid) MnSOD mRNA, in crease in MnSOD immunoreactive protein, and a three- to eightfold incr ease in MnSOD enzymatic activity, The MnSOD overexpressing cell lines became less malignant as demonstrated by requiring a higher serum conc entration to grow in vitro and much slower tumor growth in nude mice t han the parental and neo control cell lines, These findings further su pport the hypothesis that MnSOD may be a tumor suppressor gene in a ai de variety of human tumors.