CCK-B receptor-positive small cell lung cancers, breast tumors, and ovarian tumors, representIng the molecular basis of a possible autocrine

Cholecystokinin (CCK)-A and CCK.B/gastrln receptors were evalu ated with in vitro receptor autoradlography in 406 human tumors of various origins using a sulfated lasI@labelod CCK decapeptide analogue lasI.([email protected], Me@1).CCK 26-33 and *asI.Inbelod Leu15-gastrin as radioligands. CCK-B/gastrln receptors were found frequently in medul lat@r thyroid carcinomas (92%), In small cell lung cancers (57%), in astrocytomas (65%), and in stromal ovarian cancers (100%). They were found occasionally In gastroenteropancreatic tumors, breast, endometrial, and ovarian adenocarcinomas. They were either not expressed or rarely expressed In colorectal cancers, differentiated thyroid cancers, non-small cell lung cancers, meninglomas, neuroblastomas, schwannomas, glioblas tomas, lymphomas, renal cell cancers, prostate carcinomas, and the re maining neuroendocrine tumors (Le., pituitary adenomas, pheochromo cytomas, paragangilomas, and parathyroid adenomas). CCK-A receptors were expressed rarely In tumors except In gastroenteropancreatic tumors (38%), meningiomas (30%), and some neuroblastomas (19%). The iden tified CCK-A and CCK-B receptors were specific and of high affinity In the subnanomolar range. The rank order of potency of various CCK analogues was: sulfated CCK-8 L-364,718 )D nonsulfated CCK-8 L. 365,260 gastrIn for CCK-A receptors and sulfated CCK-8 > gas trin nonsulfated CCK-8 > L-365,260 > L-364,718 for CCK-B recep tors. CCK-B receptors could also be selectively and specifically labeled with a newly designed nonsulfated lasI.(D.Tyr@Gly, Nle@')-CCK 26-33. Gastrin mRNA measured by in sins hybrkllzation was present In most CCK-B receptor-positive small cell lung cancers, breast tumors, and ovarian tumors, representIng the molecular basis of a possible autocrine growth regulation of these tumors. Gastrin and CCK mRNAs were lack mg In medullary thyroid cancers. Thus, these results may have patho genie, diagnostic, differential diagnostic, and therapeutic implications.