Somatostatin receptor regulation of gastric carcinoid tumours.
Gastric carcinoids are the sequel of enterochromaffin-like (ECL) cell hyperplasia, and are usually associated with a low-acid state and hypergastrinaemia. The somatostatin (SRIF) analogue octreotide has been noted to decrease both plasma gastrin levels and ECL cell hyperplasia/neoplasia in human and rodent experimental models. The African rodent, mastomys, exhibits a genetic propensity to gastric carcinoid formation which can be significantly accelerated by acid-inhibition-induced hypergastrinaemia. Thus a low-acid state induced by either irreversible H2 blockade or proton pump inhibition shortens the natural 2-year induction time to 4 months. In vivo studies of this model demonstrate that, similar to the human situation, octreotide decreases plasma gastrin levels and inhibits low-acid-induced gastric carcinoid formation. In vitro, using isolated ECL cells, SRIF inhibits both gastrin-stimulated ECL cell histamine secretion and DNA synthesis. This mechanism appears to function via the SRIF receptor (SSTR) subtype 2, which we have identified in both naive and transformed ECL cells. Thus the direct effect of SRIF regulation of ECL cell function is mediated by at least a SSTR2 subtype. It is possible that the alteration of the SSTR2 during ECL cell transformation may contribute to the genetic susceptibility of the mastomys to carcinoid tumour formation. The precise anti-proliferative mechanism of SRIF and its role in neuroendocrine cell transformation remain to be defined. Pharmacological manipulation of the SSTR2 may provide a viable therapeutic and diagnostic target in the management not only of ECL cell neoplasia but also other types of neuroendocrine cell tumour.
Tang
L H
LH
Department of Surgery, Yale University School of Medicine, New Haven 06520-8062, USA.
Modlin
I M
IM
D000818:Animals; D002276:Carcinoid Tumor / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D017481:Receptors, Somatostatin / Q000502:physiology*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
D017481:Receptors, Somatostatin