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Differences in multidrug resistance phenotype and matrix metalloproteinases activity between endothelial cells from normal brain and glioma
Authors:Régina Anthony  Demeule Michel  Bérubé Alexandra  Moumdjian Robert  Berthelet France  Béliveau Richard
Affiliation:Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-H?pital Ste-Justine, Canada.
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.
Keywords:angiogenesis    brain tumors    endothelial cells    matrix metalloproteinases    multidrug resistance
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