Sensitivity of glioma initiating cells to a monoclonal anti-EGFR antibody therapy under hypoxia

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 dis...

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Bibliographic Details
Published in:Life sciences (1973) 2015-09, Vol.137, p.74-80
Main Authors: Randriarimanana, Tatiana, Chateau, Alicia, Faivre, Béatrice, Pinel, Sophie, Boura, Cédric
Format: Article
Language:English
Subjects:
Angiogenesis
Angiogenesis Modulating Agents - pharmacology
Anti-EGFR therapy
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - pharmacology
Antibodies, Monoclonal - therapeutic use
Brain Neoplasms - drug therapy
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Cancer
Cell Hypoxia
Cell Movement
Cell Proliferation - drug effects
Cell Survival - drug effects
Cetuximab - pharmacology
Endothelial Cells - drug effects
Gene Expression - drug effects
Glial Fibrillary Acidic Protein - metabolism
Glioma - drug therapy
Glioma - metabolism
Glioma - pathology
Glioma initiating cells
Humans
Hypoxia
Life Sciences
Neoplastic Stem Cells - drug effects
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Receptor, Epidermal Growth Factor - immunology
Stemness
Tumor Cells, Cultured
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Summary: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. 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. 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. Consequently, anti-EGFR therapy can be envisaged to target specifically GICs in order to limit the tumor recurrence.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2015.07.024