Author/Authors :
Binda، نويسنده , , Elena and Visioli، نويسنده , , Alberto and Giani، نويسنده , , Fabrizio and Lamorte، نويسنده , , Giuseppe and Copetti، نويسنده , , Massimiliano and Pitter، نويسنده , , Ken L. and Huse، نويسنده , , Jason T. and Cajola، نويسنده , , Laura and Zanetti، نويسنده , , Nadia and DiMeco، نويسنده , , Francesco and De Filippis، نويسنده , , Lidia and Mangiola، نويسنده , , Annunziato and Maira، نويسنده , , Giulio and Anile، نويسنده , , Carmelo and De Bonis، نويسنده , , Pasquale and Reynolds، نويسنده , , Brent A. and Pasquale، نويسنده , , Elena B. and Vescovi، نويسنده , , Angelo L.، نويسنده ,
Abstract :
Summary
an 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 EphA2High and EphA2Low 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.
