The EphA2 Receptor Drives Self-Renewal and Tumorigenicity in Stem-like Tumor-Propagating Cells from Human Glioblastomas

被引：193

作者：

Binda, Elena ^{[1
]}

Visioli, Alberto ^{[1
]}

Giani, Fabrizio ^{[1
]}

Lamorte, Giuseppe ^{[2
]}

Copetti, Massimiliano ^{[3
]}

Pitter, Ken L. ^{[4
]}

Huse, Jason T. ^{[5
]}

Cajola, Laura ^{[6
]}

Zanetti, Nadia ^{[6
]}

DiMeco, Francesco ^{[7
,8
]}

De Filippis, Lidia ^{[1
]}

Mangiola, Annunziato ^{[9
]}

Maira, Giulio ^{[9
]}

Anile, Carmelo ^{[9
]}

De Bonis, Pasquale ^{[9
]}

Reynolds, Brent A. ^{[10
]}

Pasquale, Elena B. ^{[11
]}

Vescovi, Angelo L. ^{[1
,3
,6
]}

机构：

[1] Univ Milano Bicocca, Dept Biotechnol & Biosci, I-20126 Milan, Italy

[2] Ist Mendel, IRCSS Casa Sollievo Sofferenza, I-00198 Rome, Italy

[3] Opera San Pio Pietralcina, IRCSS Casa Sollievo Sofferenza, I-71013 San Giovanni Rotondo, FG, Italy

[4] Weill Cornell Grad Sch Med Sci, New York, NY 10065 USA

[5] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[6] StemGen SpA, I-20126 Milan, Italy

[7] Natl Neurol Inst C Besta, I-20133 Milan, Italy

[8] Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD 21287 USA

[9] Univ Cattolica Sacro Cuore, Inst Neurosurg, I-00168 Rome, Italy

[10] Univ Florida, Program Stem Cell Biol & Regenerat Med, Evelyn F & William L McKnight Brain Inst, Ganesville, FL 32610 USA

[11] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA

来源：

CANCER CELL | 2012年 / 22卷 / 06期

关键词：

BREAST-CANCER CELLS; INITIATING CELLS; MALIGNANT GLIOMA; EPHRINA1; DIFFERENTIATION; LIGAND; INHIBITION; MULTIFORME; LEUKEMIA; THERAPY;

D O I：

10.1016/j.ccr.2012.11.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：765 / 780

页数：16

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