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

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

doi:10.1016/j.ccr.2012.11.005

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

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

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	765-780
Number of pages	16
Journal	Cancer Cell
Volume	22
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2012.11.005
Publication status	Published - Dec 11 2012

ASJC Scopus subject areas

Cancer Research
Cell Biology
Oncology

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Binda, E., Visioli, A., Giani, F., Lamorte, G., Copetti, M., Pitter, K. L., Huse, J. T., Cajola, L., Zanetti, N., DiMeco, F., De Filippis, L., Mangiola, A., Maira, G., Anile, C., De Bonis, P., Reynolds, B. A., Pasquale, E. B., & Vescovi, A. L. (2012). The EphA2 Receptor Drives Self-Renewal and Tumorigenicity in Stem-like Tumor-Propagating Cells from Human Glioblastomas. Cancer Cell, 22(6), 765-780. https://doi.org/10.1016/j.ccr.2012.11.005

Binda, E, Visioli, A, Giani, F, Lamorte, G , Copetti, M, Pitter, KL, Huse, JT, Cajola, L, Zanetti, N, DiMeco, F, De Filippis, L, Mangiola, A, Maira, G, Anile, C, De Bonis, P, Reynolds, BA, Pasquale, EB & Vescovi, AL 2012, 'The EphA2 Receptor Drives Self-Renewal and Tumorigenicity in Stem-like Tumor-Propagating Cells from Human Glioblastomas', Cancer Cell, vol. 22, no. 6, pp. 765-780. https://doi.org/10.1016/j.ccr.2012.11.005

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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 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.",

author = "Elena Binda and Alberto Visioli and Fabrizio Giani and Giuseppe Lamorte and Massimiliano Copetti and Pitter, {Ken L.} and Huse, {Jason T.} and Laura Cajola and Nadia Zanetti and Francesco DiMeco and {De Filippis}, Lidia and Annunziato Mangiola and Giulio Maira and Carmelo Anile and {De Bonis}, Pasquale and Reynolds, {Brent A.} and Pasquale, {Elena B.} and Vescovi, {Angelo L.}",

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AU - Lamorte, Giuseppe

AU - Copetti, Massimiliano

AU - Pitter, Ken L.

AU - Huse, Jason T.

AU - Cajola, Laura

AU - Zanetti, Nadia

AU - DiMeco, Francesco

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AU - Mangiola, Annunziato

AU - Maira, Giulio

AU - Anile, Carmelo

AU - De Bonis, Pasquale

AU - Reynolds, Brent A.

AU - Pasquale, Elena B.

AU - Vescovi, Angelo L.

PY - 2012/12/11

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AB - 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 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.

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

Abstract

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