Sensitivity of glioma initiating cells to a monoclonal anti-EGFR antibody therapy under hypoxia.
Fiche publication
Date publication
septembre 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PINEL Sophie, Pr BOURA Cédric
Tous les auteurs :
Randriarimanana T, Chateau A, Faivre B, Pinel S, Boura C
Lien Pubmed
Résumé
AIMS: Glioma initiating cells (GICs) represent a subpopulation of tumor cells endowed with self-renewal and multilineage differentiation capacity but also with innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in glioma patients. MATERIALS AND METHODS: In this work, GICs were obtained from two patient-derived high-grade gliomas xenograft model, expressing differently EGFR. GICs were exposed to anti-EGFR monoclonal antibody cetuximab during 48h in 1% or 21% oxygen tension. Cell viability and self-renewal capacity were then evaluated as well as their angiogenic properties. KEY FINDINGS: GICs were sensitive to cetuximab only in normoxic condition whatever the EGFR status. Nevertheless, under hypoxia cetuximab was able to decrease the self-renewal capacity as well as the expression of CD133 while expression of GFAP increased. Moreover, cetuximab decreased the effect of GICs on endothelial cell migration under hypoxia. SIGNIFICANCE: Consequently, anti-EGFR therapy can be envisaged to target specifically GICs in order to limit the tumor recurrence.
Référence
Life Sci. 2015 Sep 15;137:74-80