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


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 calcitonin-secreting 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.
Blaker
Michael
M
Medizinische Kernklinik und Poliklinik, Universitatsklinikum Hamburg-Eppendorf, Germany.
de Weerth
Andreas
A
Tometten
Mareike
M
Schulz
Martina
M
Höppner
Wolfgang
W
Arlt
Dorit
D
Hoang-Vu
Cuong
C
Dralle
Henning
H
Terpe
Harald
H
Jonas
Ludwig
L
von Schrenck
Tammo
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D019898:Autocrine Communication / Q000502:physiology; D018276:Carcinoma, Medullary / Q000378:metabolism* / Q000473:pathology; D002766:Cholecystokinin / Q000378:metabolism; D005260:Female; D005755:Gastrins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009857:Oncogenes / Q000235:genetics; D010418:Pentagastrin; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology
D005755:Gastrins; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D010418:Pentagastrin