Phenotypic modification of human glioma

Abstract

Clinical usage of glucocorticoid hormones in the reduction of intra-cerebral pressure in cases of glioma has suggested that they may also have a cytostatic effect (Lieberman et al., 1977). Investiga-tion of the effect of glucocorticoids in vitro demon-strated that although they were cytostatic at high cell densities that they are also capable of inducing cell survival and increasing clonal growth at low cell densities (Freshney et al., 1980a). Their cytostatic effect appears to be limited to high cell densities and is non-cytotoxic. Cells isolated from the plateau phase of the growth cycle following treatment with glucocorticoids showed no diminu-tion in survival in spite of a reduction in saturation density. That the reduction in saturation density is a real limitation in cell proliferation is demon-strated by a reduction in labelling index achievable by such glucocorticoids as betamethasone, dexa-methasone and methyl prednisolone. However cells isolated from such growth arrest and replated in the presence of the same concentration of hor-mone show enhanced plating efficiency and clonal growth as previously demonstrated without prior treatment. This suggested that the glucocorticoid hormones may exhibit a regulatory effect on the growth of glioma cells in culture. Chromatography on Biogel P10 of protease digests of the cell surface of cultures derived from human glioma demon-strates that the glycopeptides present on the sur-face of glioma contain more rapidly eluting pep-tides than those in normal glia (Glimelius et al., 1979). When glioma cultures are treated with glucocorticoids at 2.5 x 10⁻⁵M, approximately the maximum clinically achievable dose, then there is a reduction in the rapidly eluting peptides (Freshney et al., 1980b), denoting high sialation, observed in glioma, and the elution pattern on Biogel P10 chro-matography resembles more closely the pattern observed with normal glia.