Expression of the cholecystokinin 2-receptor in normal human thyroid gland and medullary thyroid carcinoma

Abstract

Objective: The cholecystokinin 2 -receptor (CCK 2 R) 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 CCK 2 R 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 immunohistochemistry using calcitonin-and CCK 2 R-specific antibodies on MTCs and samples of C-cell hyperplasia. Results: We demonstrate for the first time that CCK 2 R is expressed not only in MTCs but in all samples of normal thyroid tissue. Using immunohistochemistry the receptor could be localized on calcitoninsecreting C-cells. The highest incidence of CCK 2 R expression in MTCs was observed in early-tumor stages, whereas CCK 2 R could not be detected in advanced or metastasized tumors. Conclusions: The expression of CCK 2 R 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 CCK 2 R scintigraphy for the detection of MTC lesions might have to consider a lower incidence of the receptor in advanced tumor stages.

The RET Kinase Inhibitor NVP-AST487 Blocks Growth and Calcitonin Gene Expression through Distinct Mechanisms in Medullary Thyroid Cancer Cells

“…28), which may explain the brisk calcitonin response to pentagastrin seen in patients with MTC. There are indications that CCK 2 R is also expressed in normal parafollicular C cells (29). Glucagon-like peptide I also induces calcitonin mRNA in rat MTC cells (30).…”

Paracrine Regulation of Thyroid-Hormone Synthesis by C Cells

“…Recently, its receptor CCK2R, which is shared with gastrin, has been described to be expressed at different intensities in normal and malignant C cells by Blakër et al [218]. No additional data has been published with regard to the putative functional role of CCK signalling in thyroid, however, there are initial encouraging therapeutic results with the use of CCK/Gastrin R2-binding peptides in patients with MTC [219,220].…”

Skeletal effects of a gastrin receptor antagonist in H+/K+ATPase beta subunit KO mice

“…Gastrin receptors have been detected in C-cells of the thyroid gland (Blaker et al 2002) and in the brain (Lee et al 1993), but have to our knowledge not been identified in bone. In the current study, PCR analyses of gastrin receptor expression in primary mouse osteoblasts and osteoclasts were also negative.…”