Somatostatin inhibits the activity of adenylate cyclase in cultured human meningioma cells and stimulates their growth.
It has been reported previously that most human meningiomas have receptors for somatostatin. Here we report the results of investigations of the effect of somatostatin and the somatostatin analog octreotide on the growth in vitro of human meningioma cells. Neither somatostatin nor its analog showed a direct growth inhibitory action on cultured human meningioma cells. Rather, there was a slight but significant stimulation of growth in the presence of somatostatin. The somatostatin receptors in meningioma tissue were shown to be functional since somatostatin inhibited forskolin-stimulated formation of cAMP by meningioma membranes. In addition, cAMP inhibited the growth of cultured meningioma cells. We conclude that the stimulation by somatostatin of the growth of human meningioma cells in vitro is caused by its inhibitory effect on cAMP formation. These results suggest that therapeutic trials of patients with (recurrent) inoperable meningiomas with somatostatin analogs have to be carried out with great caution.
Koper
J W
JW
Department of Medicine, Erasmus University Rotterdam, The Netherlands.
Markstein
R
R
Kohler
C
C
Kwekkeboom
D J
DJ
Avezaat
C J
CJ
Lamberts
S W
SW
Reubi
J C
JC
D000067956:Adenylyl Cyclase Inhibitors; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008577:Meningeal Neoplasms / Q000201:enzymology / Q000473:pathology*; D008579:Meningioma / Q000201:enzymology / Q000473:pathology*; D015282:Octreotide / Q000494:pharmacology; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000378:metabolism / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000067956:Adenylyl Cyclase Inhibitors; D007093:Imidazoles; D007328:Insulin; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D005576:Colforsin; D013004:Somatostatin; D004815:Epidermal Growth Factor; D003994:Bucladesine; C029899:imidazole; D000242:Cyclic AMP; D015282:Octreotide; D013936:Thymidine