title: Tumor and endothelial cell hybrids participate in glioblastoma vasculature.
abstract: BACKGROUND
  Recently antiangiogenic therapy with bevacizumab has shown a high but transient efficacy in glioblastoma (GBM). Indeed, GBM is one of the most angiogenic human tumors and endothelial proliferation is a hallmark of the disease. We therefore hypothesized that tumor cells may participate in endothelial proliferation of GBM.
  
  
  METHODS
  We used EGFR FISH Probe to detect EGFR amplification and anti-CD31, CD105, VE-cadherin, and vWF to identify endothelial cells. Endothelial and GBM cells were grown separately, labeled with GFP and DsRed lentiviruses, and then cocultured with or without contact.
  
  
  RESULTS
  In a subset of GBM tissues, we found that several tumor endothelial cells carry EGFR amplification, characteristic of GBM tumor cells. This observation was reproduced in vitro: when tumor stem cells derived from GBM were grown in the presence of human endothelial cells, a fraction of them acquired endothelial markers (CD31, CD105, VE-cadherin, and vWF). By transduction with GFP and DsRed expressing lentiviral vectors, we demonstrate that this phenomenon is due to cell fusion and not transdifferentiation.
  
  
  CONCLUSIONS
  A fraction of GBM stem cells thus has the capacity to fuse with endothelial cells and the resulting hybrids may participate in tumor microvascular proliferation and in treatment resistance.
authors.affiliation: Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France.
authors.forename: Soufiane
authors.initials: S
authors.lastname: El Hallani
authors.affiliation: UMR911-CRO2, Faculté de Médecine de la Timone, Université de la Méditerranée, 13000 Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Colin
authors.affiliation: Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France.
authors.forename: Younas
authors.initials: Y
authors.lastname: El Houfi
authors.affiliation: Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France ; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, 75013 Paris, France.
authors.forename: Ahmed
authors.identifier: 0000-0001-5290-1204
authors.initials: A
authors.lastname: Idbaih
authors.affiliation: Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France.
authors.forename: Blandine
authors.initials: B
authors.lastname: Boisselier
authors.affiliation: Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Marie
authors.affiliation: Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravassard
authors.affiliation: Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Labussière
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neuropathologie Raymond Escourolle, 75013 Paris, France.
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.affiliation: Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France.
authors.forename: Jean-Léon
authors.initials: JL
authors.lastname: Thomas
authors.affiliation: Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France ; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, 75013 Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.affiliation: INSERM U833, Collège de France, 75005 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Eichmann
authors.affiliation: Sorbonne Universités, UPMC, Université Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013 Paris, France ; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie Mazarin, 75013 Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001932:Brain Neoplasms / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D018920:Coculture Techniques; D000071063:Endoglin; D042783:Endothelial Cells / Q000166:cytology*; D066246:ErbB Receptors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000098:blood supply*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008833:Microcirculation; D009369:Neoplasms / Q000473:pathology*; D009389:Neovascularization, Pathologic; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D000071063:Endoglin; D066246:ErbB Receptors; D049452:Green Fluorescent Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D000099152:Cadherin 5; C064206:ENG protein, human