Buchumschlag

Inositol-requiring enzyme 1α is a key regulator of angiogenesis and invasion in malignant glioma

Inositol-requiring enzyme 1 (IRE1) is a proximal endoplasmic reticulum (ER) stress sensor and a central mediator of the unfolded protein response. In a human glioma model, inhibition of IRE1α correlated with down-regulation of prevalent proangiogenic factors such as VEGF-A, IL-1β, IL-6, and IL-8. Si...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Auf, Gregor (VerfasserIn) , Jabouille, Arnaud (VerfasserIn) , Guérit, Sylvaine (VerfasserIn) , Pineau, Raphaël (VerfasserIn) , Delugin, Maylis (VerfasserIn) , Bouchecareilh, Marion (VerfasserIn) , Magnin, Noël (VerfasserIn) , Favereaux, Alexandre (VerfasserIn) , Maitre, Marlène (VerfasserIn) , Gaiser, Timo (VerfasserIn) , Deimling, Andreas von (VerfasserIn) , Czabanka, Marcus (VerfasserIn) , Vajkoczy, Peter (VerfasserIn) , Chevet, Eric (VerfasserIn) , Bikfalvi, Andreas (VerfasserIn) , Moenner, Michel (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: August 11, 2010
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2010, Jahrgang: 107, Heft: 35, Pages: 15553-15558
ISSN:1091-6490
DOI:10.1073/pnas.0914072107
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.0914072107
Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/doi/full/10.1073/pnas.0914072107
Volltext
Verfasserangaben:Gregor Auf, Arnaud Jabouille, Sylvaine Guérit, Raphaël Pineau, Maylis Delugin, Marion Bouchecareilh, Noël Magnin, Alexandre Favereaux, Marlène Maitre, Timo Gaiser, Andreas von Deimling, Marcus Czabanka, Peter Vajkoczy, Eric Chevet, Andreas Bikfalvi, and Michel Moenner
Beschreibung
Zusammenfassung:Inositol-requiring enzyme 1 (IRE1) is a proximal endoplasmic reticulum (ER) stress sensor and a central mediator of the unfolded protein response. In a human glioma model, inhibition of IRE1α correlated with down-regulation of prevalent proangiogenic factors such as VEGF-A, IL-1β, IL-6, and IL-8. Significant up-regulation of antiangiogenic gene transcripts was also apparent. These transcripts encode SPARC, decorin, thrombospondin-1, and other matrix proteins functionally linked to mesenchymal differentiation and glioma invasiveness. In vivo, using both the chick chorio-allantoic membrane assay and a mouse orthotopic brain model, we observed in tumors underexpressing IRE1: (i) reduction of angiogenesis and blood perfusion, (ii) a decreased growth rate, and (iii) extensive invasiveness and blood vessel cooption. This phenotypic change was consistently associated with increased overall survival in glioma-implanted recipient mice. Ectopic expression of IL-6 in IRE1-deficient tumors restored angiogenesis and neutralized vessel cooption but did not reverse the mesenchymal/infiltrative cell phenotype. The ischemia-responsive IRE1 protein is thus identified as a key regulator of tumor neovascularization and invasiveness.
Beschreibung:Gesehen am 28.11.2022
Beschreibung:Online Resource
ISSN:1091-6490
DOI:10.1073/pnas.0914072107

Ähnliche Einträge