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Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2018; 24(36): 4119-4131
Published online Sep 28, 2018. doi: 10.3748/wjg.v24.i36.4119
Calcium-sensing receptor in colorectal inflammation and cancer: Current insights and future perspectives
Luca Iamartino, Taha Elajnaf, Enikö Kallay, Martin Schepelmann
Luca Iamartino, Taha Elajnaf, Enikö Kallay, Martin Schepelmann, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna 1090, Austria
Author contributions: Iamartino L and Elajnaf T contributed equally to this paper with literature review, tables, drafting, and revision of the manuscript; Iamartino L drew the figures; Kallay E contributed to this paper with conception, revision and editing of the manuscript; Schepelmann M contributed to this paper with literature review, conception, drafting, revision and editing of the manuscript; all authors approved the final version.
Supported by the European Union’s Horizon 2020 research and innovation programme, No. 675228; and the Austrian Science Fund (FWF), No. P 29948-B28.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Martin Schepelmann, PhD, Postdoctoral Fellow, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Vienna 1090, Austria. martin.schepelmann@meduniwien.ac.at
Telephone: +61-743-14040051230 Fax: +61-743-14040051300
Received: May 30, 2018
Peer-review started: May 30, 2018
First decision: July 6, 2018
Revised: July 11, 2018
Accepted: August 1, 2018
Article in press: August 1, 2018
Published online: September 28, 2018
Processing time: 118 Days and 9.9 Hours
Abstract

The extracellular calcium-sensing receptor (CaSR) is best known for its action in the parathyroid gland and kidneys where it controls body calcium homeostasis. However, the CaSR has different roles in the gastrointestinal tract, where it is ubiquitously expressed. In the colon, the CaSR is involved in controlling multiple mechanisms, including fluid transport, inflammation, cell proliferation and differentiation. Although the expression pattern and functions of the CaSR in the colonic microenvironment are far from being completely understood, evidence has been accumulating that the CaSR might play a protective role against both colonic inflammation and colorectal cancer. For example, CaSR agonists such as dipeptides have been suggested to reduce colonic inflammation, while dietary calcium was shown to reduce the risk of colorectal cancer. CaSR expression is lost in colonic malignancies, indicating that the CaSR is a biomarker for colonic cancer progression. This dual anti-inflammatory and anti-tumourigenic role of the CaSR makes it especially interesting in colitis-associated colorectal cancer. In this review, we describe the clinical and experimental evidence for the role of the CaSR in colonic inflammation and colorectal cancer, the intracellular signalling pathways which are putatively involved in these actions, and the possibilities to exploit these actions of the CaSR for future therapies of colonic inflammation and cancer.

Keywords: Calcium-sensing receptor; Colon; Cancer; Inflammation; Calcimimetics; Calcilytics

Core tip: The extracellular calcium-sensing receptor (CaSR) is best known for its roles in maintaining body calcium homeostasis, but it is also expressed in the intestines where it is assumed to be involved in pathologies such as inflammatory bowel disease and colorectal cancer. It has been suggested to act as a tumour suppressor in colorectal tumourigenesis. In this review we highlight the evidence for the anti-inflammatory and anti-tumourigenic roles of the CaSR, its signalling pathways, and its potential for future use as a drug target in the context of inflammatory bowel disease and colorectal cancer.