CHOLECYSTOKININ (CCK)-A AND CCK-B GASTRIN RECEPTORS IN HUMAN TUMORS

Cholecystokinin (CCK)-A and CCK-B/gastrin receptors were evaluated wit h in vitro receptor autoradiography in 406 human tumors of various ori gins using a sulfated I-125-labeled CCK decapeptide analogue I-125-(D- Tyr-Gly, Nle(28,31))-CCK 26-33 and I-125-labeled Leu(15)-gastrin as ra dioligands, CCK-B/gastrin receptors were found frequently in medullary thyroid carcinomas (92%), in small cell lung cancers (57%), in astroc ytomas (65%), and in stromal ovarian cancers (100%), They were found o ccasionally in gastroenteropancreatic tumors, breast, endometrial, and ovarian adenocarcinomas. They were either not expressed or rarely exp ressed in colorectal cancers, differentiated thyroid cancers, non-smal l cell lung cancers, meningiomas, neuroblastomas, schwannomas, gliobla stomas, lymphomas, renal cell cancers, prostate carcinomas, and the re maining neuroendocrine tumors (i.e., pituitary adenomas, pheochromocyt omas, paragangliomas, and parathyroid adenomas). CCK-A receptors were expressed rarely in tumors except in gastroenteropancreatic tumors (38 %), meningiomas (30%), and some neuroblastomas (19%). The identified C CK-A and CCK-B receptors were specific and of high affinity in the sub nanomolar range. The rank order of potency of various CCK analogues wa s: sulfated CCK-8 = L-364,718 much greater than nonsulfated CCK-8 = L- 365,260 greater than or equal to gastrin for CCK-A receptors and sulfa ted CCK-8 > gastrin = nonsulfated CCK-8 > L-365,260 > L-364,718 for CC K-B receptors, CCK-B receptors could also be selectively and specifica lly labeled with a newly designed nonsulfated I-125-(D-Tyr-Gly, Nle(28 ,31))-CCK 26-33. Gastrin mRNA measured by in situ hybridization was pr esent in most CCK-B receptor-positive small cell lung cancers, breast tumors, and ovarian tumors, representing the molecular basis of a poss ible autocrine growth regulation of these tumors, Gastrin and CCK mRNA s were lacking in medullary thyroid cancers. Thus, these results may h ave pathogenic, diagnostic, differential diagnostic, and therapeutic i mplications.