Open AccessReduced Glioma Growth Following Dexamethasone or Anti‐Angiopoietin 2 Treatment
Author(s) -
Villeneuve Jérôme,
Galarneau Hugo,
Beaudet MarieJosée,
Tremblay Pierrot,
Chernomoretz Ariel,
Vallières Luc
Publication year - 2008
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2008.00139.x
Subject(s) - dexamethasone , glioma , cytotoxic t cell , cancer research , angiogenesis , in vitro , cd8 , in vivo , angiopoietin receptor , pharmacology , medicine , chemistry , biology , immune system , immunology , biochemistry , microbiology and biotechnology
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.