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

Università Cattolica del Sacro Cuore

Risultato della ricerca: Contributo in rivista › Articolo in rivista

138 Citazioni (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.

Lingua originale	English
pagine (da-a)	765-780
Numero di pagine	16
Rivista	Cancer Cell
Volume	22
DOI	https://doi.org/10.1016/j.ccr.2012.11.005
Stato di pubblicazione	Pubblicato - 2012

Keywords

Ephrin
glioblastoma
neural cancer stem cell

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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, 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 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.",

keywords = "Ephrin, glioblastoma, neural cancer stem cell, Ephrin, glioblastoma, neural cancer stem cell",

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.}",

year = "2012",

doi = "10.1016/j.ccr.2012.11.005",

language = "English",

volume = "22",

pages = "765--780",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

}

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, pagg. 765-780. https://doi.org/10.1016/j.ccr.2012.11.005

TY - JOUR

T1 - The EphA2 receptor drives self-renewal and tumorigenicity in stem-like tumor-propagating cells from human glioblastomas

AU - Binda, Elena

AU - Visioli, Alberto

AU - Giani, Fabrizio

AU - Lamorte, Giuseppe

AU - Copetti, Massimiliano

AU - Pitter, Ken L.

AU - Huse, Jason T.

AU - Cajola, Laura

AU - Zanetti, Nadia

AU - Dimeco, Francesco

AU - De Filippis, Lidia

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

Y1 - 2012

N2 - 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.

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 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.

KW - Ephrin

KW - glioblastoma

KW - neural cancer stem cell

KW - Ephrin

KW - glioblastoma

KW - neural cancer stem cell

UR - http://hdl.handle.net/10807/41595

U2 - 10.1016/j.ccr.2012.11.005

DO - 10.1016/j.ccr.2012.11.005

M3 - Article

SN - 1535-6108

VL - 22

SP - 765

EP - 780

JO - Cancer Cell

JF - Cancer Cell

ER -

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

Abstract

Keywords

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