[Regulation of cell proliferation by somatostatin].
Somatostatin and its stable analogues (octreotide, lanreotide and vapreotide) exert an antiproliferative effect on various normal and cancerous cells both in vitro and in vivo. This effect results from different mechanisms: an indirect effect by the inhibition of release of growth factors and trophic hormones (GH, IGF-1, insulin, gastrin, EGF), an inhibition of angiogenesis processes (endothelial cell proliferation, VEGF release, monocyte activity), an immunomodulatory effect (lymphocyte proliferation, interleukine or cytokine release, NK activity) and a direct effect on target cells. This direct antiproliferative effect is mediated through specific somatostatin receptors. Among them, sst(1), sst(2), sst(4) and sst(5) have been implicated in vitro in the G1-G0 cell cycle blockade, sst(3) and sst(2) mediating the apoptotic effect of somatostatin. In addition, sst(2) acts as an antioncogene in human pancreatic cancer cells. Coupling to membrane tyrosine phosphatases (SHP-1, SHP-2) is the main transduction pathway involved in the antiproliferative effect mediated by sst receptors. The dissociation observed clinically between a frequent antisecretory response and an inconstant antitumor effect after administration of somatostatin analogues may reflect an absence of expression or coupling of the receptor(s) involved in antiproliferative effect. Moreover, a desensitization or mutation of these receptors may also occur in tumors. All the potential mechanism involved should be elucidated in order to improve or better target the antitumor effect of somatostatin analogues clinically used.
Buscail
L
L
INSERM U531 et Service de Gastro-entérologie et Nutrition, CHU Rangueil, 1, avenue Jean Poulhès, 31403 Toulouse Cedex 4, France.
Vernejoul
F
F
Faure
P
P
Torrisani
J
J
Susini
C
C
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D017481:Receptors, Somatostatin / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*
D006727:Hormone Antagonists; D017481:Receptors, Somatostatin; D013004:Somatostatin