Interaction of acidic fibroblast growth factor and transforming growth factor-beta in normal and transformed glia in vitro.

Abstract

The mitogenic and morphological effects of acidic fibroblast growth factor (aFGF) and transforming growth factor-beta (TGF-beta) were assessed on cultured fetal rat astrocytes and C6 rat glioma cells in the presence and absence of serum. Astrocytes incubated with aFGF exhibited an increase in mitotic activity and characteristic morphological changes involving extensive process formation and rounding of cell bodies. Astrocytes incubated with TGF-beta underwent a slight decrease in mitotic activity and remained morphologically unchanged. Cells exposed to a combination of aFGF and TGF-beta demonstrated an attenuation of both the mitogenic and morphological changes observed in the presence of aFGF alone. The C6 glioma cells cultured in the presence of aFGF underwent a characteristic morphological change from a rounded piling cell mass to a more spindle-shaped bipolar cell layer, accompanied by an increase in mitotic activity. In contrast to the astrocyte cultures, increased growth and similar morphological effects were produced by TGF-beta. The combination of aFGF and TGF-beta did not result in attenuation of the mitogenic and morphological changes (as seen in astrocytic cells). These results suggest that, in normal fetal rat astrocytes, TGF-beta is capable of attenuating the mitogenic and morphological changes induced by aFGF in vitro. In the transformed C6 glioma cell line, aFGF and TGF-beta elicit similar mitogenic and morphological changes, without evidence of an antagonistic interaction as seen in normal astrocytes.