title: Down-regulation of caveolin-1 in glioma vasculature: modulation by radiotherapy.
abstract: Primary brain tumors, particularly glioblastomas (GB), remain a challenge for oncology. An element of the malignant brain tumors' aggressive behavior is the fact that GB are among the most densely vascularized tumors. To determine some of the molecular regulations occuring at the brain tumor endothelium level during tumoral progression would be an asset in understanding brain tumor biology. Caveolin-1 is an essential structural constituent of caveolae that has been implicated in mitogenic signaling, oncogenesis, and angiogenesis. In this work we investigated regulation of caveolin-1 expression in brain endothelial cells (ECs) under angiogenic conditions. In vitro, brain EC caveolin-1 is down-regulated by angiogenic factors treament and by hypoxia. Coculture of brain ECs with tumoral cells induced a similar down-regulation. In addition, activation of the p42/44 MAP kinase is demonstrated. By using an in vivo brain tumor model, we purified ECs from gliomas as well as from normal brain to investigate possible regulation of caveolin-1 expression in tumoral brain vasculature. We show that caveolin-1 expression is strikingly down-regulated in glioma ECs, whereas an increase of phosphorylated caveolin-1 is observed. Whole-brain radiation treatment, a classical way in which GB is currently being treated, resulted in increased caveolin-1 expression in tumor isolated ECs. The level of tumor cells spreading around newly formed blood vessels was also elevated. The regulation of caveolin-1 expression in tumoral ECs may reflect the tumoral vasculature state and correlates with angiogenesis kinetics.
authors.affiliation: Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Régina
authors.affiliation: Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Jodoin
authors.affiliation: Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Khoueir
authors.affiliation: Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
authors.forename: Yannève
authors.initials: Y
authors.lastname: Rolland
authors.affiliation: Département de Pathologie, Hôpital Notre-Dame, Montréal, Québec, Canada.
authors.forename: France
authors.initials: F
authors.lastname: Berthelet
authors.affiliation: Département de Pathologie, Hôpital Notre-Dame, Montréal, Québec, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Moumdjian
authors.affiliation: Laboratoire Mixte Institut Pasteur de Lille, Université d'Artois, Lens Cedex, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Fenart
authors.affiliation: Laboratoire Mixte Institut Pasteur de Lille, Université d'Artois, Lens Cedex, France.
authors.forename: Romeo
authors.initials: R
authors.lastname: Cecchelli
authors.affiliation: Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Demeule
authors.affiliation: Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Béliveau
mesh_terms: D042501:Angiogenic Proteins / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000532:radiotherapy; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism* / Q000528:radiation effects; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D005910:Glioma / Q000098:blood supply* / Q000378:metabolism / Q000532:radiotherapy; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000528:radiation effects; D009362:Neoplasm Metastasis / Q000503:physiopathology / Q000532:radiotherapy; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000503:physiopathology / Q000532:radiotherapy; D010766:Phosphorylation / Q000528:radiation effects; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D042501:Angiogenic Proteins; C495541:Cav1 protein, mouse; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D019950:Mitogen-Activated Protein Kinase 1