The Properties of An Immature Glial Cell Line (HITS Glioma) Derived from Ethylnitrosourea (ENU)-Induced Rat Glioma

In order to evaluate the proliferation and differentiation potentials of ethylnitrosourea (ENU)-induced glioma cells, the author attempted to obtain a cell line that maintains glial features in long term culture. One of five cell lines cultivated from ENU-induced rat gliomas deserved particular interest because of the differentiation of the neoplastic glia. This cell line, designated as HITS glioma, had a polygonal cell body and formed a monolayer with pileup foci in vitro, in contrast to the other cell lines, which showed a mesenchymal drift through passages. GFAP-positive cells, found in the primary culture, disappeared in the late passages of HITS glioma as they did in the other cell lines. Galactocerebroside (GC) and GD3 ganglioside were not expressed in the cell lines during culture. Subcutaneous inoculation of HITS glioma into neonatal rats induced tumors with various histopathological components mimicking the histopathological appearance of ENU-induced gliomas. The components also had a fraction of GFAP-positive cells. These findings indicate that HITS glioma cells may be composed of immature glial cells and differentiate into astrocytic cells under certain conditions. Insulin-like growth factor I (IGF-I), which promoted the proliferation of GFAP-positive cells in neonatal glia, was used to evaluate the mechanism(s) of proliferation and/or differentiation of HITS glioma. IGF-I did not induce the expression of GFAP in HITS glioma, even though it promoted the proliferation of HITS glioma. Although the mechanism involving the astrocytic differentiation of HITS glioma is unknown, HITS glioma may serve as a research tool in evaluating the mechanisms of proliferation and differentiation of neoplastic glia.