CD90 expression controls migration and predicts dasatinib response in glioblastoma

Tony Avril, Amandine Etcheverry, Raphaël Pineau, Joanna Obacz, Gwénaële Jegou, Florence Jouan, Pierre Jean Le Reste, Masumeh Hatami, Rivka R. Colen, Brett L. Carlson, Paul A. Decker, Jann N Sarkaria, Elodie Vauléon, Dan Cristian Chiforeanu, Anne Clavreul, Jean Mosser, Eric Chevet, Véronique Quillien

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Abstract

Purpose: CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear. Experimental Design: The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines, in vivo orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells. Results: We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/ migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes in vivo. Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion in vivo and killed CD90high primary GSC lines. Conclusions: Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90high GBM patients.

Original languageEnglish (US)
Pages (from-to)7360-7374
Number of pages15
JournalClinical Cancer Research
Volume23
Issue number23
DOIs
StatePublished - Dec 1 2017

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Glioblastoma
Stem Cells
Dasatinib
Transcriptome
Heterografts
Neoplasms
Glycoproteins
Research Design
Biomarkers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Avril, T., Etcheverry, A., Pineau, R., Obacz, J., Jegou, G., Jouan, F., ... Quillien, V. (2017). CD90 expression controls migration and predicts dasatinib response in glioblastoma. Clinical Cancer Research, 23(23), 7360-7374. https://doi.org/10.1158/1078-0432.CCR-17-1549

CD90 expression controls migration and predicts dasatinib response in glioblastoma. / Avril, Tony; Etcheverry, Amandine; Pineau, Raphaël; Obacz, Joanna; Jegou, Gwénaële; Jouan, Florence; Le Reste, Pierre Jean; Hatami, Masumeh; Colen, Rivka R.; Carlson, Brett L.; Decker, Paul A.; Sarkaria, Jann N; Vauléon, Elodie; Chiforeanu, Dan Cristian; Clavreul, Anne; Mosser, Jean; Chevet, Eric; Quillien, Véronique.

In: Clinical Cancer Research, Vol. 23, No. 23, 01.12.2017, p. 7360-7374.

Research output: Contribution to journalArticle

Avril, T, Etcheverry, A, Pineau, R, Obacz, J, Jegou, G, Jouan, F, Le Reste, PJ, Hatami, M, Colen, RR, Carlson, BL, Decker, PA, Sarkaria, JN, Vauléon, E, Chiforeanu, DC, Clavreul, A, Mosser, J, Chevet, E & Quillien, V 2017, 'CD90 expression controls migration and predicts dasatinib response in glioblastoma', Clinical Cancer Research, vol. 23, no. 23, pp. 7360-7374. https://doi.org/10.1158/1078-0432.CCR-17-1549
Avril, Tony ; Etcheverry, Amandine ; Pineau, Raphaël ; Obacz, Joanna ; Jegou, Gwénaële ; Jouan, Florence ; Le Reste, Pierre Jean ; Hatami, Masumeh ; Colen, Rivka R. ; Carlson, Brett L. ; Decker, Paul A. ; Sarkaria, Jann N ; Vauléon, Elodie ; Chiforeanu, Dan Cristian ; Clavreul, Anne ; Mosser, Jean ; Chevet, Eric ; Quillien, Véronique. / CD90 expression controls migration and predicts dasatinib response in glioblastoma. In: Clinical Cancer Research. 2017 ; Vol. 23, No. 23. pp. 7360-7374.
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abstract = "Purpose: CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear. Experimental Design: The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines, in vivo orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells. Results: We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/ migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes in vivo. Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion in vivo and killed CD90high primary GSC lines. Conclusions: Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90high GBM patients.",
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T1 - CD90 expression controls migration and predicts dasatinib response in glioblastoma

AU - Avril, Tony

AU - Etcheverry, Amandine

AU - Pineau, Raphaël

AU - Obacz, Joanna

AU - Jegou, Gwénaële

AU - Jouan, Florence

AU - Le Reste, Pierre Jean

AU - Hatami, Masumeh

AU - Colen, Rivka R.

AU - Carlson, Brett L.

AU - Decker, Paul A.

AU - Sarkaria, Jann N

AU - Vauléon, Elodie

AU - Chiforeanu, Dan Cristian

AU - Clavreul, Anne

AU - Mosser, Jean

AU - Chevet, Eric

AU - Quillien, Véronique

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Purpose: CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear. Experimental Design: The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines, in vivo orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells. Results: We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/ migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes in vivo. Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion in vivo and killed CD90high primary GSC lines. Conclusions: Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90high GBM patients.

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