Interrelationship between differentiation and malignancy-associated properties in glioma.

The phenotypic expression of cells derived from human anaplastic astrocytomas, rat glioma, normal human adult and foetal brain tissue have been examined for differentiated and malignancy-associated properties. Glial fibrillary acidic protein (GFAP), high affinity glutamate and gamma-amino butyric acid (GABA) uptake and glutamine synthetase were used as indicators of astroglial differentiation. Plasminogen activator and tumour angiogenesis factor were the malignancy-associated markers. The normal adult brain-derived lines showed some differentiated astroglial features and expressed low levels of the malignancy-associated properties. The foetal cultures contained highly differentiated astroglia while the glioma lines showed considerable phenotypic heterogeneity from highly differentiated to undifferentiated. The least differentiated glioma cells exhibited the highest plasminogen activator activities. The density-dependent control of phenotypic expression was also investigated. High affinity GABA uptake, and GFAP in rat C6 glioma cultures, increased with increasing monolayer cell density, events probably mediated by an increase in the formation of cell-cell contacts at confluence. Plasminogen activator activity decreased with increasing cell density.