Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1277, Jiefang Avenue, Jiangan District, Wuhan, 430022, PR China.
Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, No.13, Hangkong Road, Qiaokou District, Wuhan, 430030, PR China.
Sci Rep. 2018 Jan 18;8(1):1076. doi: 10.1038/s41598-018-19286-1.
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 ([Ca]) 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.
研究表明钙敏感受体（CaSR）参与了多种人类癌症的进展。然而，CaSR 在子宫内膜癌中的作用尚不清楚。本研究初步分析了 CaSR 对子宫内膜癌发展的影响。通过慢病毒转染（CaSR-OV）异位表达 CaSR 在 Ishikawa 细胞中显著增加了细胞内钙离子（[Ca]）水平和细胞凋亡。与对照 Ishikawa 细胞（载体）相比，CaSR-OV Ishikawa 细胞中 E-钙粘蛋白和β-连环蛋白的表达和膜上复合物的形成增加。此外，CaSR-OV Ishikawa 细胞的侵袭潜能降低，这归因于 E-钙粘蛋白/β-连环蛋白复合物的形成。此外，免疫组织化学显示，与正常标本相比，子宫内膜癌中 CaSR 的表达降低，并且与 E-钙粘蛋白表达呈正相关，而与β-连环蛋白表达无关。此外，在 CaSR-OV Ishikawa 细胞中 VEGFR3 的表达显著下调。此外，免疫组织化学分析显示，与正常子宫内膜相比，子宫内膜癌中 VEGFR3 的表达显著增加，并且与 CaSR 表达呈负相关。然而，CaSR 敲低产生了相反的效果。这些发现表明 CaSR 在子宫内膜癌中具有抑制作用。因此，CaSR 表达降低可能是子宫内膜癌进展的一个合适的解释和有价值的预测指标。
