School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
Biochim Biophys Acta Rev Cancer. 2021 Apr;1875(2):188528. doi: 10.1016/j.bbcan.2021.188528. Epub 2021 Feb 26.
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 (Ca) 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 Ca 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.
癌症是全球发病率和死亡率的主要原因，因为它能够逃避免疫监视并从起源部位转移到继发部位。尽管已经开发了几种治疗技术来抑制或控制癌症的扩散，但一种完全控制疾病的策略仍然让研究人员难以捉摸。在考虑控制或预防癌症转移到骨骼的方法时，我们分析了钙敏感受体（CaSR）的影响，其主要作用是维持细胞和全身生理过程中的钙（Ca）稳态。CaSR 是一种多效受体，能够增强某些癌症的增殖，如乳腺癌、肺癌、前列腺癌和肾癌在其主要部位，并刺激骨转移，而在其他癌症如结肠癌中则发挥抑制作用。CaSR 的活性不仅增加了所指出的器官中癌细胞的增殖、迁移和凋亡抑制，还增加了甲状旁腺激素相关蛋白（PTHrP）和表皮调节素的分泌，这诱导溶骨性活性和成骨抑制。此外，从骨吸收中释放的细胞因子和 Ca 是进一步促进癌症增殖的关键因素。在这篇综述中，我们试图强调以前关于 CaSR 的观点，讨论其在新背景下的作用，并考虑其在癌症治疗中的潜在临床应用。
