Reduced Glioma Growth Following Dexamethasone or Anti-Angiopoietin 2 Treatment
Source: http://blackwell-synergy.com/doi/abs/10.1111/…
Jérôme Villeneuve; Hugo Galarneau; Marie-Josée Beaudet; Pierrot Tremblay; Ariel Chernomoretz*; Luc Vallières
Department of Oncology and Molecular Endocrinology, Laval University Hospital Research Center, Québec City, Québec, Canada.
* Current address: Departamento de Fisica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon 1 Ciudad Universitaria, 1428, Buenos Aires, Argentina
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.
