IN-VITRO GROWTH-INHIBITION OF GROWTH FACTOR-STIMULATED MENINGIOMA CELLS BY CALCIUM-CHANNEL ANTAGONISTS

STUDIES HAVE SHOWN that a majority of meningiomas contain receptors fo r platelet-derived growth factor and epidermal growth factor and that these growth factors promote the proliferation of meningioma cells in culture. Although the mechanism of action has not been elucidated, int racellular calcium appears to be part of the signal transduction mecha nism. Because alterations in intracellular calcium could interrupt thi s pathway and decrease cellular proliferation, we investigated the eff ects of calcium channel-blocking agents on the growth of meningioma ce lls in vitro. Primary meningioma cell cultures were established, and t he cells were characterized by light and electron microscopy and by im munohistochemical studies. Then, the cultures were given growth factor s and/or various calcium channel antagonists, and growth rates were me asured. A dose-response decrease in cell growth was seen when verapami l, nifedipine, or diltiazem (voltage-dependent calcium channel-blockin g agents) was added to serum-containing media. Also, these drugs block ed the growth stimulation of epidermal growth factor and platelet-deri ved growth factor in a similar fashion. Dantrolene, which inhibits the release of sequestered intracellular calcium, was also an effective b locker of the mitogenic stimulation of these growth factors.