title: The EphA2 receptor drives self-renewal and tumorigenicity in stem-like tumor-propagating cells from human glioblastomas.
abstract: In human glioblastomas (hGBMs), tumor-propagating cells with stem-like characteristics (TPCs) represent a key therapeutic target. We found that the EphA2 receptor tyrosine kinase is overexpressed in hGBM TPCs. Cytofluorimetric sorting into EphA2(High) and EphA2(Low) populations demonstrated that EphA2 expression correlates with the size and tumor-propagating ability of the TPC pool in hGBMs. Both ephrinA1-Fc, which caused EphA2 downregulation in TPCs, and siRNA-mediated knockdown of EPHA2 expression suppressed TPCs self-renewal ex vivo and intracranial tumorigenicity, pointing to EphA2 downregulation as a causal event in the loss of TPCs tumorigenicity. Infusion of ephrinA1-Fc into intracranial xenografts elicited strong tumor-suppressing effects, suggestive of therapeutic applications.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milan Bicocca, 20126 Milan, Italy. elena.binda@unimib.it
authors.forename: Elena
authors.initials: E
authors.lastname: Binda
authors.forename: Alberto
authors.initials: A
authors.lastname: Visioli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lamorte
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Ken L
authors.initials: KL
authors.lastname: Pitter
authors.forename: Jason T
authors.initials: JT
authors.lastname: Huse
authors.forename: Laura
authors.initials: L
authors.lastname: Cajola
authors.forename: Nadia
authors.initials: N
authors.lastname: Zanetti
authors.forename: Francesco
authors.initials: F
authors.lastname: DiMeco
authors.forename: Lidia
authors.initials: L
authors.lastname: De Filippis
authors.forename: Annunziato
authors.initials: A
authors.lastname: Mangiola
authors.forename: Giulio
authors.initials: G
authors.lastname: Maira
authors.forename: Carmelo
authors.initials: C
authors.lastname: Anile
authors.forename: Pasquale
authors.initials: P
authors.lastname: De Bonis
authors.forename: Brent A
authors.initials: BA
authors.lastname: Reynolds
authors.forename: Elena B
authors.initials: EB
authors.lastname: Pasquale
authors.forename: Angelo L
authors.initials: AL
authors.lastname: Vescovi
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D036382:Ephrin-A1 / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques / Q000379:methods; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D036104:Receptor, EphA2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D036382:Ephrin-A1; D036104:Receptor, EphA2