The suppressive role of calcium sensing receptor in endometrial cancer

Abstract

Studies have shown that calcium sensing receptor (CaSR) is involved in the progressions of several human cancers. However, the role of CaSR in endometrial cancer remains unknown. This study provides a preliminary analysis of the CaSR effect on endometrial cancer development. Ectopic CaSR expression by lentiviral transfection (CaSR-OV) in Ishikawa cells significantly increased intracellular calcium ([Ca2+]i) levels and cell apoptosis. E-cadherin and β-catenin expression and complex formation at the membrane were increased in CaSR-OV Ishikawa cells relative to control Ishikawa cells (vector). Furthermore, CaSR-OV Ishikawa cells showed a reduced invasive potential, which was attributed to E-cadherin/β-catenin complex formation. Moreover, a reduction in CaSR expression in endometrial cancer relative to normal specimens was evident by immunohistochemistry and was positively associated with E-cadherin, but not β-catenin, expression. Furthermore, VEGFR3 was significantly down-regulated in CaSR-OV Ishikawa cells. Additionally, an immunohistochemical analysis showed that VEGFR3 was significantly increased in endometrial cancer compared with the normal endometrium and was inversely correlated with CaSR expression. However, the CaSR knockdown produced the opposite effects. These findings suggest an inhibitory role for CaSR in endometrial cancer. Therefore, reduced CaSR expression may be a suitable explanation and valuable predictor for endometrial cancer progression.

Genome-wide analysis of cervical secretions obtained during embryo transfer reveals the association between deoxyribonucleic acid methylation and pregnancy outcomes

“…CASR encodes a calcium-sensing receptor, which is a plasma membrane G protein-coupled receptor involved in calcium homeostasis (48). In human endometrium, CASR was reported to play an inhibitory role in endometrial cancer (49). CASR protein is only expressed in epithelial cells, which mediates the secretion of stanniocalcin-1, a glycoprotein significantly up-regulated in midsecretory endometrial fluid of fertile endometrium (50).…”

Two Birds, One Stone: Double Hits on Tumor Growth and Lymphangiogenesis by Targeting Vascular Endothelial Growth Factor Receptor 3

“…VEGFR3 has also been shown to be expressed in neuronal progenitors, osteoblasts, and macrophages [50,51,52]. Furthermore, recent studies have indicated that VEGFR3 expression is detected in different types of cancers and it contributes to tumor progression and lymphatic metastasis (Table 1) [53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93].…”

“…Immunohistochemical analysis and qRT-PCR studies have demonstrated that the expression of VEGFR3 was increased in endometrial carcinomas compared with normal endometrium [64,65]. Additionally, VEGFR3 expression was significantly associated with tumor stage and poor disease-free survival in endometrial carcinomas [64].…”

Calcium Sensing Receptor Inhibits Growth of Human Lung Adenocarcinoma Possibly via the GSK3β/Cyclin D1 Pathway

“…Consistently, in a clinical study with large sample sizes and long follow-up periods, Yang et al (2018) found that CaSR-positive expression status was essential for the antineoplastic effect of calcium in colorectal cancer (Yang et al, 2018). Our previous work showed that CaSR activation reduced cell viability and induced apoptosis in endometrial cancer (Xin et al, 2018). These discrepancies of the roles of CaSR on tumor progression among different types of cancers imply that it might be tissue or disease specific.…”