title: Cholecystokinin(CCK)-A and CCK-B/gastrin receptors in human tumors.
abstract: Cholecystokinin (CCK)-A and CCK-B/gastrin receptors were evaluated with in vitro receptor autoradiography in 406 human tumors of various origins using a sulfated 125I-labeled CCK decapeptide analogue 125I-(D-Tyr-Gly, Nle28,3l)-CCK 26-33 and 125I-labeled Leu15-gastrin as radioligands. CCK-B/gastrin receptors were found frequently in medullary 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, meningiomas, neuroblastomas, schwannomas, glioblastomas, lymphomas, renal cell cancers, prostate carcinomas, and the remaining neuroendocrine tumors (i.e., pituitary adenomas, pheochromocytomas, 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 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 >> nonsulfated CCK-8 = L-365,260 > or = gastrin for CCK-A receptors and sulfated CCK-8 > gastrin = nonsulfated CCK-8 > L-365,260 > L-364,718 for CCK-B receptors. CCK-B receptors could also be selectively and specifically labeled with a newly designed nonsulfated 125I-(D-Tyr-Gly, Nle28,31)-CCK 26-33. Gastrin mRNA measured by in situ hybridization 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 lacking in medullary thyroid cancers. Thus, these results may have pathogenic, diagnostic, differential diagnostic, and therapeutic implications.
authors.affiliation: Division of Cell Biology and Experimental Cancer Research, University of Berne, Switzerland.
authors.forename: J C
authors.initials: JC
authors.lastname: Reubi
authors.forename: J C
authors.initials: JC
authors.lastname: Schaer
authors.forename: B
authors.initials: B
authors.lastname: Waser
mesh_terms: D001345:Autoradiography; D001943:Breast Neoplasms / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005755:Gastrins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D018358:Neuroendocrine Tumors / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012844:Sincalide / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism
chemical_list: D005755:Gastrins; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D012844:Sincalide