In Vitro Growth Inhibition of Growth Factor-stimulated Meningioma Cells by Calcium Channel Antagonists

Abstract

Studies have shown that a majority of meningiomas contain receptors for 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, intracellular calcium appears to be part of the signal transduction mechanism. Because alterations in intracellular calcium could interrupt this pathway and decrease cellular proliferation, we investigated the effects of calcium channel-blocking agents on the growth of meningioma cells in vitro. Primary meningioma cell cultures were established, and the cells were characterized by light and electron microscopy and by immunohistochemical studies. Then, the cultures were given growth factors and/or various calcium channel antagonists, and growth rates were measured. A dose-response decrease in cell growth was seen when verapamil, nifedipine, or diltiazem (voltage-dependent calcium channel-blocking agents) was added to serum-containing media. Also, these drugs blocked the growth stimulation of epidermal growth factor and platelet-derived growth factor in a similar fashion. Dantrolene, which inhibits the release of sequestered intracellular calcium, was also an effective blocker of the mitogenic stimulation of these growth factors.

Expression of hypoxia inducible factor—1 alpha and correlation with preoperative embolization of meningiomas

“…Establishment of primary meningioma cultures has been previously described in detail. 15,16 Briefly, meningiomas were taken immediately from the operating room, digested with collagenase, and placed in modified Eagle medium containing 10% fetal bovine serum. Only passages 1 and 2 were used in experiments for this study.…”

The biology of meningiomas

“…Black et al have reported that increasing the concentration of PDGF in meningiomas in culture causes them to grow, but only to the point at which a sufficiently high concentration saturates the system [34]. Calcium-channel blockers have been used in combination with PD GF in meningiomas in culture to determine if PDGF exerts its effect through the calciumdependent second-messenger systems that transmit the effect of receptor perturbation from the cell membrane to the nucleus [35]. The receptor for PDGF exists in a-and b-subunits that combine together to form aa, ab, and bb isoforms, whereas PDGF itself has "A" and "B" subunits.…”

Molecular Biology of Unreresectable Meningiomas: Implications for New Treatments and Review of the Literature

“…111,112 These studies arose out of the observation that calcium is an integral component of the intracellular signaling pathways. It was hypothesized that calcium channel antagonists might interrupt this signaling with subsequent growth inhibition.…”