Differences in multidrug resistance phenotype and matrix metalloproteinases activity between endothelial cells from normal brain and glioma.
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.
Régina
Anthony
A
Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste-Justine, Canada.
Demeule
Michel
M
Bérubé
Alexandra
A
Moumdjian
Robert
R
Berthelet
France
F
Béliveau
Richard
R
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000943:Antigens, Differentiation; D014408:Biomarkers, Tumor; D020782:Matrix Metalloproteinases