OGR1 与肿瘤微环境
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(1.国家卫生健康委员会人类疾病比较医学重点实验室,北京市人类重大疾病实验动物模型工程技术研究中心,中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,北京 100021; 2.首都医科大学附属北京同仁医院,北京 100730)

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R-33

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OGR1 and the tumor microenvironment
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(1. NHC Key Laboratory of Human Disease Comparative Medicine; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases; Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing 100021, China. 2. Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing 100730)

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    摘要:

    肿瘤微环境曾被认为对肿瘤的生长和侵袭作用是微小的,现今人们已认识到其在肿瘤发展中扮演的角色是不可或缺的?肿瘤的一个共性是缺氧,低氧亦是肿瘤微环境的代表性特征之一,这些特性致使肿瘤细胞外氢离子浓度上升,pH 下降(酸中毒),形成特异的酸性微环境?该酸性微环境不仅对肿瘤细胞的增殖?迁移?侵袭?转移和治疗有重要影响;同时对免疫细胞,血管细胞和其他基质细胞的功能也具有一定作用?然而,肿瘤细胞感知和响应微环境中酸性pH 的分子机制尚不清楚?有研究表明,有些受体和离子通道家族可以帮助细胞感知酸中毒,作为G 蛋白偶联受体家族(G-protein coupled receptors,GPCRs)成员的卵巢癌G 蛋白偶联受体1(OGR1)主要作用是由酸中毒激活并介导多个下游G 蛋白信号传导途径,不仅可以调节肿瘤细胞转移和增殖,对免疫细胞的功能,炎症和血管形成也具有重要影响?本文论述了OGR1 与肿瘤发生及其与肿瘤微环境,免疫反应和血管生成之间的关系?近些年来,GPCRs 作为主要的药物靶标,对其pH 敏感的GPCR 小分子调节剂的开发已经成为研究热点?而对OGR1 与肿瘤微环境相互作用之间的研究将为肿瘤的治疗和化学预防提供新策略?

    Abstract:

    The tumor microenvironment was once considered to have little effect on tumor growth and invasion.However, it has now been recognized that it plays an indispensable role in tumor development. One of the commoncharacteristics of tumors is hypoxia, which is also one of the representative characteristics of the tumor microenvironment.Hypoxia leads to an increase in extracellular hydrogen ion concentrations, a decrease in pH (acidosis), and the formationof a specific acidic microenvironment. The acidic microenvironment plays an important role not only in the proliferation,migration, invasion, metastasis and treatment of cancer cells, but also in the function of immune cells, vascular cells andother stromal cells. However, the molecular mechanism through which tumor cells perceive and respond to acidic pH intheir microenvironment remains unclear. Previous studies have shown that some receptors and ion channel families can helpcells to perceive acidosis. As a G-protein coupled receptor (GPCR), ovarian cancer G-protein coupled receptor 1 (OGR1)is activated by acidosis and mediates several downstream G-protein signal transduction pathways. It can not only regulatemetastasis and proliferation in cancer cells, but also plays an important role in the function of immune cells, inflammationand angiogenesis. In the current review, the effects of OGR1 in tumorigenesis, the tumor microenvironment, the immuneresponse and angiogenesis are discussed. The development of small molecule regulators targeting GPCRs has become an areaof active research in recent years. Studying the interaction between OGR1 and the tumor microenvironment will provide new strategies for cancer treatment and chemoprevention.

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李维莎,刘宏飞,严立波,高苒,秦川. OGR1 与肿瘤微环境[J].中国比较医学杂志,2019,29(7):96~101.

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  • 收稿日期:2019-01-30
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  • 在线发布日期: 2019-08-01
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自2024年1期开始,杂志参考文献改为中英文对照,具体格式要求可置下载中心查看!
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