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 taken 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 conditions via Western blot analysis and immunocytochemical staining using a panel of antibodies specific for major myelin markers and glial fibrillary acidic protein. In low serum conditions, the clones resemble immature oligodendrocytes and express only immature oligodendrocyte markers. When placed in serum-free chemically defined medium (CDM), nine clones do not change their phenotypes, while five variably express myelin markers. One clone, 4C8, differentiates into mature, membrane sheet-bearing oligodendrocyte-like cells and expresses major myelin markers in amounts and distributions similar to cultured primary oligodendrocytes. Our data show that 4C8 can reversibly switch from an oligodendrocyte-like phenotype to a reactive astrocyte-like phenotype, depending upon the presence of serum and other factors in different growth media. Our data indicate that serum "pushes" 4C8 into the astrocyte-like phenotype, while serum-free CDM "pushes" 4C8 into the oligodendrocyte-like phenotype. Furthermore, a population of mixed phenotypes results when the astrocyte-like 4C8 cells are placed in serum-free CDM. To our knowledge, this is the first report to show that by altering environment, a "mixed glioma" can arise from a homogeneous population of glial tumor cells. It is therefore possible that glial tumor cells in vivo may be induced to undergo similar phenotypic changes when they are exposed to different environmental signals in the central nervous system.