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 which this growth inhibition is mediated.


METHODS
Primary cell cultures from patients with intracranial meningiomas were established. Cell growth studies were performed with inhibitors and stimulators of tyrosine kinase signal transduction. Intracellular calcium changes and inositol phosphate production were measured after growth factor exposure, 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 can stimulate or inhibit the growth of in vitro meningiomas, respectively. Calcium channel antagonists inhibit intracellular calcium changes induced by serum and epidermal growth factor. Inositol phosphate production is increased after growth factor stimulation, and calcium channel antagonists potentiate this effect.


CONCLUSIONS
Calcium channel antagonists interfere with intracellular signaling 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 relevant strategies for growth inhibition.
Jensen
R L
RL
Department of Neurosurgery, University of Utah, Salt Lake City 84112, USA.
Petr
M
M
Wurster
R D
RD
D000328:Adult; D000368:Aged; D001790:Blood Physiological Phenomena; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D046508:Culture Techniques; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008577:Meningeal Neoplasms / Q000503:physiopathology*; D008579:Meningioma / Q000503:physiopathology*; D008875:Middle Aged; D011799:Quinazolines; D015398:Signal Transduction / Q000187:drug effects*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D006133:Growth Substances; D007295:Inositol Phosphates; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D004815:Epidermal Growth Factor; D010738:Type C Phospholipases; D002118:Calcium