| DOI | Trouver le DOI : https://doi.org/10.1038/onc.2008.287 |
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| Auteur | Rechercher : Pen, A.1; Rechercher : Moreno, M. J.1; Rechercher : Durocher, Y.2; Rechercher : Deb-Rinker, P.1; Rechercher : Stanimirovic, D. B.1 |
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| Affiliation | - Conseil national de recherches du Canada. Institut des sciences biologiques du CNRC
- Conseil national de recherches du Canada. Institut de recherche en biotechnologie du CNRC
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| Format | Texte, Article |
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| Sujet | biotechnology; blood supply; brain; capillaries; cell line, tumor; cell; cells, cultured; cerebrovascular circulation; culture media; culture media, conditioned; cytology; drug effects; endothelial cells; endothelium, vascular; enzyme-linked immunosorbent assay; gene expression regulation, neoplastic; genetics; glioblastoma; insulin-like growth factor binding proteins; neovascularization, pathologic; pharmacology; phosphorylation; physiology; protein; proteins; RNA; RNA, messenger; secretion; signal transduction; smad2 protein; transforming growth factor beta |
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| Résumé | Insulin-like growth factor-binding protein 7 (IGFBP7) is a selective biomarker of glioblastoma (GBM) vessels, strongly expressed in tumor endothelial cells and vascular basement membrane. IGFBP7 gene regulation and its potential role in tumor angiogenesis remain unclear. Mechanisms of IGFBP7 induction and its angiogenic capacity were examined in human brain endothelial cells (HBECs) exposed to tumor-like conditions. HBEC treated with GBM cell (U87MG)-conditioned media (-CM) exhibited fourfold upregulation of IGFBP7 mRNA and protein compared to control cells. IGFBP7 gene regulation in HBEC was methylation independent. U87MG-CM analysed by enzyme-linked immunosorbent assay contained ~5 pm transforming growth factor (TGF)-β1, a concentration sufficient to stimulate IGFBP7 in HBEC to similar levels as U87MG-CM. Both pan-TGF-β-neutralizing antibody (1D11) and the TGF-β1 receptor (activin receptor-like kinase 5, ALK5) antagonist, SB431542, blocked U87MG-CM-induced IGFBP7 expression in HBEC, indicating that TGF-β1 is an important tumor-secreted effector capable of IGFBP7 induction in endothelial cells. HBEC exposed to either U87MG-CM or IGFBP7 protein exhibited increased capillary-like tube (CLT) formation in Matrigel. Both TGF-β1- and U87MG-CM-induced Smad-2 phosphorylation and U87MG-CM-induced CLT formation in HBEC were inhibited by the ALK5 antagonist, SB431542. These data suggest that proangiogenic IGFBP7 may be induced in brain endothelial cells by TGF-βs secreted by GBM, most likely through TGF-β1/ALK5/Smad-2 pathway. |
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| Date de publication | 2008-08-18 |
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| Dans | |
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| Langue | anglais |
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| Numéro du CNRC | NRCC 52721 |
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| Numéro NPARC | 9364383 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | 89800e29-27b5-4751-8215-47390cc25607 |
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| Enregistrement créé | 2009-07-10 |
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| Enregistrement modifié | 2020-04-15 |
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