Autocrine regulation of glial proliferation and differentiation: the induction of cytodifferentiation of postmitotic normal glioblast by growth-promoting factor from astrocytoma cell.

A growth-promoting factor (GPF) from astrocytoma cells (GA-1) cultured in serum-free medium (N2) exerted on normal glioblasts proliferative and differentiation-promoting effects, which have been observed in glia maturation factor (GMF) stimulation. The serum-free conditioned media of GA-1 provoked DNA synthesis of glioblasts, and subsequently elicited a morphological differentiation characterized by the extrusion of processes as well as biochemical changes including an increased cellular level of glia fibrillary acidic protein (GFA protein), S-100 protein, and alpha-enolase. The transforming growth factor activity was also found in the media. Partially purified GPF had a molecular weight range of 7100-10,000 Mr and acidic isoelectric point (pH 4.6), and showed a susceptibility to heat treatment and denaturation at low and high pHs. The present results and the findings accumulated from our previous studies on gliotrophic growth factors provide a general concept of the growth and differentiation regulations of normal or neoplastic glial cells by growth factors through autocrine systems.