Down-regulation of caveolin-1 in glioma vasculature: modulation by radiotherapy.
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.
Régina
Anthony
A
Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
Jodoin
Julie
J
Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
Khoueir
Paul
P
Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
Rolland
Yannève
Y
Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
Berthelet
France
F
Département de Pathologie, Hôpital Notre-Dame, Montréal, Québec, Canada.
Moumdjian
Robert
R
Département de Pathologie, Hôpital Notre-Dame, Montréal, Québec, Canada.
Fenart
Laurence
L
Laboratoire Mixte Institut Pasteur de Lille, Université d'Artois, Lens Cedex, France.
Cecchelli
Romeo
R
Laboratoire Mixte Institut Pasteur de Lille, Université d'Artois, Lens Cedex, France.
Demeule
Michel
M
Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
Béliveau
Richard
R
Laboratoire de Médecine Moléculaire, Université du Québec à Montréal-Hôpital Ste.-Justine, Montréal, Québec, Canada.
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
D042501:Angiogenic Proteins; C495541:Cav1 protein, mouse; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D019950:Mitogen-Activated Protein Kinase 1