A CLONE OF THE MOCH-1 GLIAL TUMOR IN CULTURE - MULTIPLE PHENOTYPES EXPRESSED UNDER DIFFERENT ENVIRONMENTAL-CONDITIONS

The MOCH-1 glial cell line, which was derived from a glioblastoma take n from the brain of a MBP/c-neu transgenic mouse, was used as a model for studying the plastic nature of gliomas in culture. Fifteen MOCH-1 clones were derived and characterized under different growth condition s via Western blot analysis and immunocytochemical staining using a pa nel of antibodies specific for major myelin markers and glial fibrilla ry acidic protein. In low serum conditions, the clones resemble immatu re oligodendrocytes and express only immature oligodendrocyte markers. When placed in serum-free chemically defined medium (CDM), nine clone s do not: change their phenotypes, while five variably express myelin markers. One clone, 4C8, differentiates into mature, membrane sheer-be aring oligodendrocyte-like cells and expresses major myelin markers in amounts and distributions similar to cultured primary oligodendrocyte s. Our data show that 4C8 can reversibly switch from an oligodendrocyt e-like phenotype to a reactive astrocyte-like phenotype, depending upo n the presence of serum and other factors in different growth media. O ur data indicate that serum ''pushes'' 4C8 into the astrocyte-like phe notype, while serum-free CDM ''pushes'' 4C8 into the oligodendrocyte-l ike phenotype. Furthermore, a population of mixed phenotypes results w hen the astrocyte-like 4C8 cells are placed in serum-free CDM. To our knowledge, this is the first report to show that by altering environme nt, a ''mixed glioma'' can arise from a homogeneous population of glia l tumor cells, It is therefore possible that glial tumor cells in vivo may be induced to undergo similar phenotypic changes when they are ex posed to different environmental signals in the central nervous system .