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正常脑内皮细胞与胶质瘤内皮细胞在多药耐药表型及基质金属蛋白酶活性方面的差异。

Differences in multidrug resistance phenotype and matrix metalloproteinases activity between endothelial cells from normal brain and glioma.

作者信息

Régina Anthony, Demeule Michel, Bérubé Alexandra, Moumdjian Robert, Berthelet France, Béliveau Richard

机构信息

Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste-Justine, Canada.

出版信息

J Neurochem. 2003 Jan;84(2):316-24. doi: 10.1046/j.1471-4159.2003.01521.x.

DOI:10.1046/j.1471-4159.2003.01521.x
PMID:12558994
Abstract

Endothelial cells (ECs) are new targets for tumor therapy. In this work, we purified endothelial cells from intracerebral and subcutaneous experimental gliomas as well as from normal brain in order to define some of the phenotypical differences between angiogenic and quiescent brain vasculature. We show that the multidrug resistance genes encoding drug efflux pumps at the brain endothelium are expressed differently in normal and tumoral vasculature. We also show that ECs from gliomas present increased activity of gelatinase B (MMP9), key enzyme in the angiogenic process. Importantly, we observe a different phenotype between ECs in the intracerebral and subcutaneous models. Our results provide molecular evidence of phenotypic distinction between tumoral and normal brain vasculature and indicate that the EC phenotype depends on interactions both with tumor cells and also with the microenvironment.

摘要

内皮细胞(ECs)是肿瘤治疗的新靶点。在本研究中,我们从脑内和皮下实验性胶质瘤以及正常脑组织中纯化内皮细胞,以确定血管生成性和静止性脑血管之间的一些表型差异。我们发现,编码脑内皮细胞药物外排泵的多药耐药基因在正常和肿瘤血管中的表达不同。我们还发现,胶质瘤来源的内皮细胞中明胶酶B(MMP9)的活性增加,MMP9是血管生成过程中的关键酶。重要的是,我们观察到脑内和皮下模型中的内皮细胞存在不同的表型。我们的结果提供了肿瘤和正常脑血管之间表型差异的分子证据,并表明内皮细胞表型取决于与肿瘤细胞以及微环境的相互作用。

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引用本文的文献

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Propentofylline decreases tumor growth in a rodent model of glioblastoma multiforme by a direct mechanism on microglia.丙戊茶碱通过对小神经胶质细胞的直接作用抑制多形性胶质母细胞瘤啮齿动物模型中的肿瘤生长。
Neuro Oncol. 2012 Feb;14(2):119-31. doi: 10.1093/neuonc/nor194. Epub 2011 Nov 15.
2
Current review of in vivo GBM rodent models: emphasis on the CNS-1 tumour model.目前对体内 GBM 啮齿动物模型的综述:重点介绍 CNS-1 肿瘤模型。
ASN Neuro. 2011 Aug 3;3(3):e00063. doi: 10.1042/AN20110014.
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Identification of novel vascular markers through gene expression profiling of tumor-derived endothelium.
通过肿瘤来源内皮细胞的基因表达谱鉴定新型血管标志物。
BMC Genomics. 2008 Apr 30;9:201. doi: 10.1186/1471-2164-9-201.
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Brain endothelial cells as pharmacological targets in brain tumors.脑内皮细胞作为脑肿瘤的药理学靶点。
Mol Neurobiol. 2004 Oct;30(2):157-83. doi: 10.1385/MN:30:2:157.
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Brain Pathol. 2003 Oct;13(4):482-94. doi: 10.1111/j.1750-3639.2003.tb00479.x.