Unexpected high incidence of cholecystokinin-B/gastrin receptors in human medullary thyroid carcinomas

Abstract

The 2 gastrointestinal peptides cholecystokinin (CCK) and gastrin, which act through CCK-A receptors (having high affinity for CCK) or CCK-B/gastrin receptors (having high affinity for CCK and gastrin), are considered to be important tumor growth factors. We have evaluated CCK-A and CCK-B/gastrin receptors in 34 human thyroid cancers using in vitro receptor autoradiography with 2 different radioligands. We demonstrate high-affinity CCK-B/gastrin receptors in medullary thyroid carcinomas, present at very high incidence (92%) but the absence of these receptors in non-medullary thyroid carcinomas or in normal thyroid glands. CCK-B/gastrin receptors are therefore likely to be the molecular substrate for the pentagastrin-stimulation test, widely used in medullary thyroid carcinomas; moreover, they represent the targets for physiologically secreted gastrin or CCK which, as growth factors, may stimulate the growth of medullary thyroid carcinomas. Furthermore, these results have diagnostic as well as therapeutic implications: radiolabeled gastrin and CCK analogs may be used for scintigraphic tumor localization in vivo, whereas CCK-B-selective antagonists may be of therapeutic value.