| DOI | Trouver le DOI : https://doi.org/10.1593/neo.13212 |
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| Auteur | Rechercher : Moreno, M.J.1; Rechercher : Ball, M.1; Rechercher : Rukhlova, M.1; Rechercher : Slinn, J.1; Rechercher : L'Abbe, D.1; Rechercher : Iqbal, U.1; Rechercher : Monette, R.1; Rechercher : Hagedorn, M.; Rechercher : O'Connor-McCourt, M.D.1; Rechercher : Durocher, Y.1; Rechercher : Stanimirovic, D.B.1 |
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| Affiliation | - Conseil national de recherches du Canada
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| Format | Texte, Article |
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| Sujet | cathepsin B; somatomedin binding protein 1; somatomedin binding protein 4; angiogenesis; animal experiment; animal model; animal tissue; antiangiogenic activity; antineoplastic activity; cancer transplantation; cell anchorage; cell growth; cell viability; confocal laser microscopy; glioblastoma; human cell; male; mouse; tissue section; tumor growth |
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| Résumé | Insulin-like growth factor-binding protein 4 (IGFBP-4/IBP-4) has potent IGF-independent anti-angiogenic and antitumorigenic effects. In this study, we demonstrated that these activities are located in the IGFBP-4 C-terminal protein fragment (CIBP-4), a region containing a thyroglobulin type 1 (Tg1) domain. Proteins bearing Tg1 domains have been shown to inhibit cathepsins, lysosomal enzymes involved in basement membrane degradation and implicated in tumor invasion and angiogenesis. In our studies, CIBP-4 was shown to internalize and co-localize with lysosomal-like structures in both endothelial cells (ECs) and glioblastoma U87MG cells. CIBP-4 also inhibited both growth factor-induced EC tubulogenesis in Matrigel and the concomitant increases in intracellular cathepsin B (CatB) activity. In vitro assays confirmed CIBP-4 capacity to block recombinant CatB activity. Biodistribution analysis of intravenously injected CIBP-4-Cy5.5 in a glioblastoma tumor xenograft model indicated targeted accumulation of CIBP-4 in tumors. Most importantly, CIBP-4 reduced tumor growth in this animal model by 60%. Pleiotropic anti-angiogenic and anti-tumorigenic activities of CIBP-4 most likely underlie its observed therapeutic potential against glioblastoma. © 2013 Neoplasia Press, Inc. |
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| Date de publication | 2013 |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Numéro NPARC | 21270681 |
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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 | 47c8a2b6-dc22-4121-b871-9ed7cdd45733 |
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| Enregistrement créé | 2014-02-17 |
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| Enregistrement modifié | 2020-04-22 |
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