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代谢型谷氨酸受体:控制肿瘤生长的新靶点?

Metabotropic glutamate receptors: new targets for the control of tumor growth?

作者信息

Nicoletti Ferdinando, Arcella Antonietta, Iacovelli Luisa, Battaglia Giuseppe, Giangaspero Felice, Melchiorri Daniela

机构信息

Istituto Neurologico Mediterraneo Neuromed, Località Camerelle, Pozzilli 86079, Italy.

出版信息

Trends Pharmacol Sci. 2007 May;28(5):206-13. doi: 10.1016/j.tips.2007.03.008. Epub 2007 Apr 11.

Abstract

Cancer stem cells are currently a target for the treatment of malignant tumors. Transformed neural stem-progenitor cells of the brain subventricular zone and the external granular layer of the cerebellum are the putative cells of origin of malignant gliomas and medulloblastomas, which are the most frequent malignant brain tumors in adults and children, respectively. The proliferation of neural stem-progenitor cells is regulated by metabotropic glutamate (mGlu) receptors, which are G-protein-coupled receptors that are activated by glutamate, the major excitatory neurotransmitter of the CNS. At least two receptor subtypes - mGlu(3) and mGlu(4) receptors - control the proliferation of brain tumor cells, whereas mGlu(1) receptors have been implicated in the development of melanomas. We believe that individual mGlu receptor subtypes represent new potential targets for the treatment of several malignant tumors, including brain tumors.

摘要

癌症干细胞目前是恶性肿瘤治疗的靶点。脑室内下区和小脑外颗粒层的转化神经干细胞祖细胞分别是恶性胶质瘤和髓母细胞瘤的假定起源细胞,而恶性胶质瘤和髓母细胞瘤分别是成人和儿童中最常见的恶性脑肿瘤。神经干细胞祖细胞的增殖受代谢型谷氨酸(mGlu)受体调节,mGlu受体是G蛋白偶联受体,由中枢神经系统主要兴奋性神经递质谷氨酸激活。至少两种受体亚型——mGlu(3)和mGlu(4)受体——控制脑肿瘤细胞的增殖,而mGlu(1)受体与黑色素瘤的发生有关。我们认为,单个mGlu受体亚型是包括脑肿瘤在内的几种恶性肿瘤治疗的新潜在靶点。

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