Immunocytochemical Localization of the Extracellular Calcium-Sensing Receptor in Normal and Malignant Human Large Intestinal Mucosa

Abstract

SUMMARY We identified the parathyroid type Ca2+-sensing receptor (CaR) in normal human colon mucosa and in cancerous lesions at the mRNA and protein level. Polymerase chain reaction produced an amplification product from reverse-transcribed large intestinal RNA which corresponded in size and length to a 537-bp sequence from exon 7 of the CaR gene. With a specific antiserum against its extracellular domain, the CaR could be detected by immunostaining in normal human colon mucosa in cells preferentially located at the crypt base. The CaR protein was also expressed in tumors of the large bowel in all 20 patients examined. However, the great majority of CaR-positive cells in the adenocarcinomas inspected were confined to more differentiated areas exhibiting glandular-tubular structures. Poorly or undifferentiated regions were either devoid of specific immunoreactivity or contained only isolated CaR-positive cells. In the normal mucosa and in glandular-tubular structures of cancerous lesions, the CaR was exclusively expressed in chromogranin A-positive enteroendocrine cells and in only a small fraction of PCNA-positive cells.

Regulation of E‐cadherin and β‐catenin by Ca2+ in colon carcinoma is dependent on calcium‐sensing receptor expression and function

“…34,35 Although the findings presented here were obtained with a line of human colon carcinoma cells, the findings are likely to have implications for human colon cancer. We 8,9 and others 10 have shown in the past that expression of CaSR is reduced or lacking entirely in histological sections of colon carcinoma. Those cancers with the most anaplastic features exhibited the least CaSR.…”

Parathyroid Hormone Gene rs6256 and Calcium Sensing Receptor Gene rs1801725 Variants are not Associated with Susceptibility to Colorectal Cancer in Iran

“…It is possible that the changed expression of CaSR is associated with abnormal differentiation and or tumor progression, or both (Chakrabarty et al, 2003). The CaSR expression patterns indicate its role in the pathogenesis of CRC; the expression of CaSR is high in normal large intestinal epithelium, is lower in well-differentiated colon cancer tissue, and is greatly decreased in undifferentiated carcinomas (Gama et al, 1997;Sheinin et al, 2000). In fact, loss of the CaSR expression in colonic epithelium is a key event in the pathogenesis of colon cancer (Rogers et al, 2012).…”

Upregulation of calcium-sensing receptor and mitogen-activated protein kinase signalling in the regulation of growth and differentiation in colon carcinoma

“…Immunoperoxidase staining for E-cadherin was performed as described previously using formalin-fixed CBS cells (Sheinin et al, 2000;Chakrabarty et al, 2003). The immunoperoxidase reaction product was visualised using diaminobenzidine as the chromogenic substrate.…”