title: Differences in multidrug resistance phenotype and matrix metalloproteinases activity between endothelial cells from normal brain and glioma.
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.
authors.affiliation: Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste-Justine, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Régina
authors.forename: Michel
authors.initials: M
authors.lastname: Demeule
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bérubé
authors.forename: Robert
authors.initials: R
authors.lastname: Moumdjian
authors.forename: France
authors.initials: F
authors.lastname: Berthelet
authors.forename: Richard
authors.initials: R
authors.lastname: Béliveau
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001921:Brain / Q000098:blood supply*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D005910:Glioma / Q000098:blood supply*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000943:Antigens, Differentiation; D014408:Biomarkers, Tumor; D020782:Matrix Metalloproteinases