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-ne gative 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 induc ible GFAP expression. This experimental system creates an "on/off" situatio n in which GFAP expression is suppressed by tetracycline. Inducible express ion of GFAP in the absence of tetracycline was confirmed by immunofluoresce nce staining and Northern and Western blotting. The study showed that force d GFAP expression resulted in an inhibition of cell motility measured as th e phagokinetic track area of individual cells seeded sparsely on a surface covered with gold particles. It also resulted in a change in cell morpholog y, 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 expressio n that is often seen in gliomas in vivo may be an important parameter of tu mor progression related mainly to the motile and thereby invasive propertie s of malignant glioma cells. (C) 2000 Wiley-Liss, Inc.