The EphA2 receptor drives self-renewal and tumorigenicity in stem-like tumor-propagating cells from human glioblastomas

Annunziato Mangiola, Giulio Maira, Carmelo Anile, Pasquale De Bonis, E Binda, A Visioli, F Giani, G Lamorte, M Copetti, Kl Pitter, Jt Huse, L Cajola, N Zanetti, F Dimeco, L De Filippis, Ba Reynolds, Eb Pasquale, Al Vescovi

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138 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)765-780
Number of pages16
JournalCancer Cell
Volume22
DOIs
Publication statusPublished - 2012

Keywords

  • Ephrin
  • glioblastoma
  • neural cancer stem cell

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