Calcium channel antagonist effect on in vitro meningioma signal transduction pathways after growth factor stimulation

OBJECTIVE: We have previously demonstrated that calcium channel antagonists inhibit the growth of human meningiomas in culture after stimulation with growth factors. This study examined the effects of these drugs on signaling transduction pathways in an attempt to elucidate potential mechanisms by w hich this growth inhibition is mediated. METHODS: Primary cell cultures from patients with intracranial meningiomas were established. Cell growth studies were performed with inhibitors and st imulators of tyrosine kinase signal transduction. Intracellular calcium cha nges and inositol phosphate production were measured after growth factor ex posure, with or without pretreatment by calcium channel antagonists. RESULTS: The growth of meningiomas in culture can be inhibited by tyrosine kinase receptor inhibitors. Inhibitors and stimulators of phospholipase C c an stimulate or inhibit the growth of in vitro meningiomas, respectively. C alcium channel antagonists inhibit intracellular calcium changes induced by serum and epidermal growth factor. Inositol phosphate production is increa sed after growth factor stimulation, and calcium channel antagonists potent iate this effect. CONCLUSION: Calcium channel antagonists interfere with intracellular signal ing pathways of cultured meningioma cells. This inhibition is unrelated to voltage-sensitive calcium channels. The findings of this project may aid in the understanding of the signal transduction mechanisms involved in growth factor-mediated meningioma proliferation and may lead to clinically releva nt strategies for growth inhibition.