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The Role of the Calcium-Sensing Receptor in the Development and Progression of Cancer

Institut National de la Santé Et de la Recherche Médicale, ERI-12 (Z.S., R.M.), Université de Picardie Jules Verne, 80037 Amiens, France; and Division of Endocrinology, Diabetes and Hypertension (E.M.B.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115

Correspondence: Address all correspondence and requests for reprints to: Zuzana Saidak, Institut National de la Santé et de la Recherche Médicale ERI-12, 1, rue des Louvels, 80037 Amiens, France. E-mail: zuzana.saidak{at}gmail.com

The calcium-sensing receptor (CaR) is responsive to changes in the extracellular Ca²⁺ (Ca²⁺_o) concentration. It is a member of the largest family of cell surface receptors, the G protein-coupled receptors, and it has been shown to be involved in Ca²⁺_o homeostasis. Apart from its primary role in Ca²⁺_o homeostasis, the CaR may be involved in phenomena that allow for the development of many types of benign or malignant tumors, from parathyroid adenomas to breast, prostate, and colon cancers. For example, whereas the CaR is expressed in both normal and malignant breast tissue, increased CaR levels have been reported in highly metastatic primary breast cancer cells and breast cancer cell lines, possibly contributing to their malignancy and associated alterations in their biological properties. In these settings the CaR exhibits oncogenic properties. Enhanced CaR expression and altered proliferation of prostate cancer cells in response to increased Ca²⁺_o have also been described. In contrast, colon and parathyroid cancers often present with reduced or absent CaR expression, and activation of this receptor decreases cell proliferation, suggesting a role for the CaR as a tumor suppressor gene. Thus, the CaR may play an important role in the development of many types of neoplasia. Herein, we review the role of the CaR in various benign and malignant tumors in further detail, describing its contribution to parathyroid tumors, breast, prostate, and colon cancers, and we evaluate how pharmacological manipulations of this receptor may be of interest for the treatment of certain cancers in the future.