Role of the calcium-sensing receptor (CaSR) in cancer metastasis to bone: Identifying a potential therapeutic target

Abstract

Cancer is a major cause of morbidity and mortality worldwide due to its ability to evade immune surveillance and metastasize from its origin to a secondary point of contact. Though several treatment techniques have been developed to suppress or manage cancer spread, a strategy for total control over the disease continues to evade researchers. In considering ways to control or prevent cancer from metastasizing to the bone, we analyze the impact of the calcium-sensing receptor (CaSR), whose primary role is to maintain calcium (Ca²⁺) homeostasis in cellular and systemic physiological processes. CaSR is a pleiotropic receptor capable of enhancing the proliferation of some cancers such as breast, lung, prostate and kidney cancers at its primary site(s) and stimulating bone metastasis, while exerting a suppressive effect in others such as colon cancer. The activity of CaSR not only increases cancer cell proliferation, migration and suppression of apoptosis in the organs indicated, but also increases the secretion of parathyroid hormone-related protein (PTHrP) and epiregulin, which induce osteolytic activity and osteoblastic suppression. In addition, released cytokines and Ca²⁺ from bone resorption are critical factors that further promote cancer proliferation. In this review, we seek to highlight previous viewpoints on CaSR, discuss its role in a new context, and consider its potential clinical application in cancer treatment.

Keywords: Bone; Calcium-sensing receptor; Cancer; Metastasis; Microenvironment; Signaling; Tumor proliferation.