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: Elena Binda, Alberto Visioli, Fabrizio Giani, Giuseppe Lamorte, Massimiliano Copetti, Ken L Pitter, Jason T Huse, Laura Cajola, Nadia Zanetti, Francesco DiMeco, Lidia De Filippis, Annunziato Mangiola, Giulio Maira, Carmelo Anile, Pasquale De Bonis, Brent A Reynolds, Elena B Pasquale, Angelo L Vescovi
• Journal: Cancer cell (Cancer Cell) Vol. 22 Issue 6 Pg. 765-80 (Dec 11 2012) ISSN: 1878-3686 [Electronic] United States
• PMID: 23238013 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Ephrin-A1
• Receptor, EphA2

Topics

• Cell Differentiation (genetics)
• Cell Transformation, Neoplastic (genetics, pathology)
• Down-Regulation (genetics)
• Ephrin-A1 (genetics, metabolism)
• Gene Knockdown Techniques (methods)
• Glioblastoma (genetics, metabolism, pathology)
• Humans
• Neoplastic Stem Cells (metabolism, pathology)
• Receptor, EphA2 (genetics, metabolism)