Calcium Sensing Receptor Modulation for Cancer Therapy

Abstract

The calcium sensing receptor (CaSR) is a member of the largest family of cell surface receptors, the G protein-coupled receptors involved in calcium homeostasis. The role of the CaSR in neoplasia appears to be homeostatic; loss of normal CaSR-induced response to extracellular calcium is observed in cancers of the colon and ovary, while increased release of PTHrP is observed in cancers of the breast, prostate and Leydig cells. Currently CaSR can be considered as a molecule that can either promote or prevent tumor growth depending on the type of cancer. Therefore, recognition of the multifaceted role of CaSR in gliomas and other malignant tumors in general is fundamental to elucidating the mechanisms of tumor progression and the development of novel therapeutic agents. Emphasis should be placed on development of drug-targeting methods to modulate CaSR activity in cancer cells.Keywords: CaSR -GPCR -metastasis -PTHrP -homeostasis -cancer cells MINI-REVIEW Calcium Sensing Receptor Modulation for Cancer TherapyPuja Sarkar, Sudhir Kumar* and migration in tumor cells. Herein, we review the role of calcium sensing receptor (CaSR) in the development and metastasis of cancer and manipulation of the receptor for the treatment of cancers in the future.

Voltage-gated calcium channels: Novel targets for cancer therapy

“…Therefore, their functions are largely unknown in terms of their role in cancer progression. Notably, compared with our previous studies, CACNA1S was overexpressed relative to normal tissue samples in acute myeloid leukemia and brain and central nervous system (CNS) tumors (1). The present data revealed downregulated CACNA1S in renal oncocytoma, with a −3.920-fold change, as well as in head and neck squamous cell carcinoma, (3.670-fold change) and in squamous cell lung carcinoma (−2.038-fold change), compared with matched normal tissue (Table I).…”

“…Conventional studies on ion channels have primarily focused on the crucial roles these channels perform in excitatory cell types, including neurons, cardiomyocytes and secretory cells (1). The roles of ion channels in various cell functions, including mitogenesis, cell proliferation, differentiation, apoptosis and metastasis are now well recognized (2–4).…”

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

“…CaSR appears to play a tumor suppressor role in CRC and has a critical role in the maintenance of calcium homeostasis (Sarkar and Kumar, 2012;Ward et al, 2012) by modulating parathyroid hormone (PTH) secretion from the parathyroid glands (Saidak et al, 2009). In recent years, the relationship between CaSR gene polymorphisms and CRC risk has garnered a great deal of attention and association studies of CaSR gene rs1801725 (A986S) variant have been performed to investigate its implication with CRC risk, but despite the biological plausibility the results are inconsistent (Speer et al, 2002;Fuszek et al, 2004;Bacsi et al, 2008;Dong et al, 2008;Jenab et al, 2009) and the role of this gene in the etiology of CRC is still equivocal.…”

Tissue specific role of calcium sensing receptor

“…The CaSR has recently been documented to be expressed in a variety of benign tumor and malignancies, often at expression levels that differ from those in their healthy counterparts like in breast cancer, prostate cancer, as well as in cancers originating from organs involved in Ca 2+ homeostasis, including colorectal cancer and parathyroid adenomas (Sarkar and Kumar, 2012). A recent examination of publicly available gene expression data identified a variety of types of GPCRs (Dores and Trejo, 2012), including protease activated receptor and receptors for various chemokines, adenosine 2B, neuropeptide, metabotropic glutamate, and CaSR that are overexpressed in diverse type of cancer (Rozengurt, 2007).…”