Expression of the cholecystokinin2-receptor in normal human thyroid gland and medullary thyroid carcinoma

Objective: The cholecystokinin2-receptor (CCK2R) promotes secretion and cell growth induced by its ligands cholecystokinin (CCK) and gastrin. The receptor has recently been shown to be expressed in human medullary thyroid carcinomas (MTCs). The objective of this study was to analyze CCK2R expression in MTC samples of different tumor stages as well as in non-malignant thyroid tissues. Design and Methods: Using RT-PCR we investigated 19 MTC samples and TT-cells (a human MTC cell line), as well as samples of normal thyroid. In addition, we performed immumohistochemistry using calcitonin- and CCK2R-specific antibodies on MTCs and samples of C-cell hyperplasia. Results: We demonstrate for the first time that CCK2R is expressed not only in MTCs but in all samples of normal thyroid tissue. Using inummohistochemistry the receptor could be localized on calcitonin-secreting C-cells. The highest incidence of CCK2R expression in MTCs was observed in early-tumor stages, whereas CCK2R could not be detected in advanced or metastasized tumors. Conclusions: The expression of CCK2R in C-cells suggests a physiological function for gastrin and/or CCK in the regulation of calcitonin release, presumably related to bone and calcium metabolism. Moreover, these ligands might act as growth factors in MTCs. Efforts in the development of CCK2R scintigraphy for the detection of MTC lesions might have to consider a lower incidence of the receptor in advanced tumor stages.