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- Title
Reduced Glioma Growth Following Dexamethasone or Anti-Angiopoietin 2 Treatment.
- Authors
Villeneuve, Jérôme; Galarneau, Hugo; Beaudet, Marie-Josée; Tremblay, Pierrot; Chernomoretz, Ariel; Vallières, Luc
- Abstract
All patients with glioblastoma, the most aggressive and common form of brain cancer, develop cerebral edema. This complication is routinely treated with dexamethasone, a steroidal anti-inflammatory drug whose effects on brain tumors are not fully understood. Here we show that dexamethasone can reduce glioma growth in mice, even though it depletes infiltrating T cells with potential antitumor activity. More precisely, T cells with helper or cytotoxic function were sensitive to dexamethasone, but not those that were negative for the CD4 and CD8 molecules, including gammadelta and natural killer (NK) T cells. The antineoplastic effect of dexamethasone was indirect, as it did not meaningfully affect the growth and gene expression profile of glioma cells in vitro. In contrast, hundreds of dexamethasone-modulated genes, notably angiopoietin 2 (Angpt2), were identified in cultured cerebral endothelial cells by microarray analysis. The ability of dexamethasone to attenuate Angpt2 expression was confirmed in vitro and in vivo. Selective neutralization of Angpt2 using a peptide-Fc fusion protein reduced glioma growth and vascular enlargement to a greater extent than dexamethasone, without affecting T cell infiltration. In conclusion, this study suggests a mechanism by which dexamethasone can slow glioma growth, providing a new therapeutic target for malignant brain tumors.
- Subjects
IMMUNITY; BRAIN tumors; GLIOBLASTOMA multiforme; GLUCOCORTICOIDS; GLIOMAS
- Publication
Brain Pathology, 2008, Vol 18, Issue 3, p401
- ISSN
1015-6305
- Publication type
Article
- DOI
10.1111/j.1750-3639.2008.00139.x