Effects of inducible glial fibrillary acidic protein on glioma cell motility and proliferation.

We have studied the effect of induced glial fibrillary acidic protein (GFAP) on motility, cell morphology, and proliferation of two originally GFAP-negative human glioma cell lines. Glioma cell lines U-1242 MG and U-251 MG sp subclone 3A were transfected with a vector system that allows for an inducible GFAP expression. This experimental system creates an "on/off" situation in which GFAP expression is suppressed by tetracycline. Inducible expression of GFAP in the absence of tetracycline was confirmed by immunofluorescence staining and Northern and Western blotting. The study showed that forced GFAP expression resulted in an inhibition of cell motility measured as the phagokinetic track area of individual cells seeded sparsely on a surface covered with gold particles. It also resulted in a change in cell morphology, with extended cell processes, and it was associated with a low fraction of cells in S-phase. We conclude that the down-regulation of GFAP expression that is often seen in gliomas in vivo may be an important parameter of tumor progression related mainly to the motile and thereby invasive properties of malignant glioma cells.