Régina Anthony, Demeule Michel, Bérubé Alexandra, Moumdjian Robert, Berthelet France, Béliveau Richard
Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste-Justine, Canada.
J Neurochem. 2003 Jan;84(2):316-24. doi: 10.1046/j.1471-4159.2003.01521.x.
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.
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。