title: Sensitivity of glioma initiating cells to a monoclonal anti-EGFR antibody therapy under hypoxia.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Consequently, anti-EGFR therapy can be envisaged to target specifically GICs in order to limit the tumor recurrence.
authors.affiliation: Université de Lorraine, CRAN, UMR 7039, Campus Science, BP 70239, 54506 Vandœuvre-lès-Nancy, France; CNRS, CRAN, UMR 7039, Vandœuvre-lès-Nancy Cedex 54506, France.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Randriarimanana
authors.affiliation: Université de Lorraine, CRAN, UMR 7039, Campus Science, BP 70239, 54506 Vandœuvre-lès-Nancy, France; CNRS, CRAN, UMR 7039, Vandœuvre-lès-Nancy Cedex 54506, France.
authors.forename: Alicia
authors.initials: A
authors.lastname: Chateau
authors.affiliation: Université de Lorraine, CRAN, UMR 7039, Campus Science, BP 70239, 54506 Vandœuvre-lès-Nancy, France; CNRS, CRAN, UMR 7039, Vandœuvre-lès-Nancy Cedex 54506, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Faivre
authors.affiliation: Université de Lorraine, CRAN, UMR 7039, Campus Science, BP 70239, 54506 Vandœuvre-lès-Nancy, France; CNRS, CRAN, UMR 7039, Vandœuvre-lès-Nancy Cedex 54506, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Pinel
authors.affiliation: Université de Lorraine, CRAN, UMR 7039, Campus Science, BP 70239, 54506 Vandœuvre-lès-Nancy, France; CNRS, CRAN, UMR 7039, Vandœuvre-lès-Nancy Cedex 54506, France. Electronic address: cedric.boura@univ-lorraine.fr.
authors.forename: Cédric
authors.initials: C
authors.lastname: Boura
mesh_terms: D043924:Angiogenesis Modulating Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000068818:Cetuximab / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D043924:Angiogenesis Modulating Agents; D000911:Antibodies, Monoclonal; D005904:Glial Fibrillary Acidic Protein; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: Angiogenesis; Anti-EGFR therapy; Glioma initiating cells; Hypoxia; Stemness