EGFRvIII mutations can emerge as late and heterogenous events in glioblastoma development and promote angiogenesis through Src activation.

Eskilsson, Eskil; Rosland, Gro V; Talasila, Krishna M; Knappskog, Stian; Keunen, Olivier; Sottoriva, Andrea; Foerster, Sarah; Solecki, Gergely; Taxt, Torfinn; Jirik, Radovan; FRITAH, Sabrina; Harter, Patrick N; Välk, Kristjan; Al Hossain, Jubayer; Joseph, Justin V; Jahedi, Roza; Saed, Halala S; Piccirillo, Sara G; Spiteri, Inma; Leiss, Lina; Euskirchen, Philipp; Graziani, Grazia; Daubon, Thomas; Lund-Johansen, Morten; Enger, Per Øyvind; Winkler, Frank; Ritter, Christoph A; NICLOU, Simone P.; Watts, Colin; Bjerkvig, Rolf; Miletic, Hrvoje

doi:10.1093/neuonc/now113

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Article (Périodiques scientifiques)

EGFRvIII mutations can emerge as late and heterogenous events in glioblastoma development and promote angiogenesis through Src activation.

Eskilsson, Eskil; Rosland, Gro V; Talasila, Krishna M et al.

2016 • In Neuro-Oncology, 18 (12), p. 1644 - 1655

Peer reviewed vérifié par ORBi

Permalien
https://hdl.handle.net/10993/60196

DOI
10.1093/neuonc/now113

PubMed
27286795

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Détails

Mots-clés :

EGFR; EGFRvIII; angiogenesis; glioblastoma; invasion; epidermal growth factor receptor VIII; EGFR protein, human; ErbB Receptors; Proto-Oncogene Proteins pp60(c-src); Brain/diagnostic imaging; Brain/pathology; Brain Neoplasms/diagnostic imaging; Brain Neoplasms/genetics; Brain Neoplasms/metabolism; Brain Neoplasms/pathology; Cell Line, Tumor; ErbB Receptors/genetics; ErbB Receptors/metabolism; Evolution, Molecular; Glioblastoma/diagnostic imaging; Glioblastoma/genetics; Glioblastoma/metabolism; Glioblastoma/pathology; Humans; Multimodal Imaging; Mutation; Neoplasm Invasiveness; Neovascularization, Pathologic/metabolism; Proto-Oncogene Proteins pp60(c-src)/metabolism; Survival Analysis; Up-Regulation; Brain; Brain Neoplasms; Neovascularization, Pathologic; Receptor, Epidermal Growth Factor; Oncology; Neurology (clinical); Cancer Research

Résumé :

[en] [en] BACKGROUND: Amplification of the epidermal growth factor receptor (EGFR) and its mutant EGFRvIII are among the most common genetic alterations in glioblastoma (GBM), the most frequent and most aggressive primary brain tumor. METHODS: In the present work, we analyzed the clonal evolution of these major EGFR aberrations in a small cohort of GBM patients using a unique surgical multisampling technique. Furthermore, we overexpressed both receptors separately and together in 2 patient-derived GBM stem cell lines (GSCs) to analyze their functions in vivo in orthotopic xenograft models. RESULTS: In human GBM biopsies, we identified EGFR amplification as an early event because EGFRvIII mutations emerge from intratumoral heterogeneity later in tumor development. To investigate the biological relevance of this distinct developmental pattern, we established experimental model systems. In these models, EGFR+ tumor cells showed activation of classical downstream signaling pathways upon EGF stimulation and displayed enhanced invasive growth without evidence of angiogenesis in vivo. In contrast, EGFRvIII+ tumors were driven by activation of the prototypical Src family kinase c-Src that promoted VEGF secretion leading to angiogenic tumor growth. CONCLUSIONS: The presented work shows that sequential EGFR amplification and EGFRvIII mutations might represent concerted evolutionary events that drive the aggressive nature of GBM by promoting invasion and angiogenesis via distinct signaling pathways. In particular, c-SRC may be an attractive therapeutic target for tumors harboring EGFRvIII as we identified this protein specifically mediating angiogenic tumor growth downstream of EGFRvIII.

Disciplines :

Neurologie

Auteur, co-auteur :

Eskilsson, Eskil; Department of Biomedicine, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., T.T., K.V., J.A.H., J.V.J., R.J., H.S.S., L.L., T.D., P.Ø.E., R.B., H.M.), KG Jebsen Brain Tumor Research Center, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., K.V., J.A.H., J.V.J., T.D., P. Ø.E., S.P.N., R.B., H.M.), Department of Clinical Science, University of Bergen, Norway (S.K.), Department of Oncology, Haukeland University Hospital, Bergen, Norway (S.K.), Norlux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (O.K., S.F., S.P.N., R.B.), Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK (A.S.), Department of Clinical Pharmacy, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany (S.F., C.A.R.), Department of Neurooncology, University Hospital Heidelberg, Germany (G.S., F.W.), Institute of Scientific Instruments, ASCR, Brno, Czech Republic (R.J.), Edinger-Intsitute, Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H.), Department of Pathology, Haukeland University Hospital, Bergen, Norway (J.A.H., H.M.), Department of Clinical Neurosciences, University of Cambridge, UK (S.G.P., C.W.), Statistics and Computational Biology Laboratory, University of Cambridge, UK (I.S.), Neuro Clinic, Haukeland University Hospital, Bergen, Norway, Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Germany (P.E.), Department of Systems Medicine, University of Rome «Tor Vergata», Rome, Italy (G.G.), INSERM U1029 - University of Bordeaux, Allée Geoffroy St. Hilaire, Pessac, France (T.D.), Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (M.L.-J., P. Ø.E

Rosland, Gro V; Department of Biomedicine, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., T.T., K.V., J.A.H., J.V.J., R.J., H.S.S., L.L., T.D., P.Ø.E., R.B., H.M.), KG Jebsen Brain Tumor Research Center, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., K.V., J.A.H., J.V.J., T.D., P. Ø.E., S.P.N., R.B., H.M.), Department of Clinical Science, University of Bergen, Norway (S.K.), Department of Oncology, Haukeland University Hospital, Bergen, Norway (S.K.), Norlux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (O.K., S.F., S.P.N., R.B.), Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK (A.S.), Department of Clinical Pharmacy, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany (S.F., C.A.R.), Department of Neurooncology, University Hospital Heidelberg, Germany (G.S., F.W.), Institute of Scientific Instruments, ASCR, Brno, Czech Republic (R.J.), Edinger-Intsitute, Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H.), Department of Pathology, Haukeland University Hospital, Bergen, Norway (J.A.H., H.M.), Department of Clinical Neurosciences, University of Cambridge, UK (S.G.P., C.W.), Statistics and Computational Biology Laboratory, University of Cambridge, UK (I.S.), Neuro Clinic, Haukeland University Hospital, Bergen, Norway, Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Germany (P.E.), Department of Systems Medicine, University of Rome «Tor Vergata», Rome, Italy (G.G.), INSERM U1029 - University of Bordeaux, Allée Geoffroy St. Hilaire, Pessac, France (T.D.), Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (M.L.-J., P. Ø.E

Talasila, Krishna M; Department of Biomedicine, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., T.T., K.V., J.A.H., J.V.J., R.J., H.S.S., L.L., T.D., P.Ø.E., R.B., H.M.), KG Jebsen Brain Tumor Research Center, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., K.V., J.A.H., J.V.J., T.D., P. Ø.E., S.P.N., R.B., H.M.), Department of Clinical Science, University of Bergen, Norway (S.K.), Department of Oncology, Haukeland University Hospital, Bergen, Norway (S.K.), Norlux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (O.K., S.F., S.P.N., R.B.), Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK (A.S.), Department of Clinical Pharmacy, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany (S.F., C.A.R.), Department of Neurooncology, University Hospital Heidelberg, Germany (G.S., F.W.), Institute of Scientific Instruments, ASCR, Brno, Czech Republic (R.J.), Edinger-Intsitute, Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H.), Department of Pathology, Haukeland University Hospital, Bergen, Norway (J.A.H., H.M.), Department of Clinical Neurosciences, University of Cambridge, UK (S.G.P., C.W.), Statistics and Computational Biology Laboratory, University of Cambridge, UK (I.S.), Neuro Clinic, Haukeland University Hospital, Bergen, Norway, Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Germany (P.E.), Department of Systems Medicine, University of Rome «Tor Vergata», Rome, Italy (G.G.), INSERM U1029 - University of Bordeaux, Allée Geoffroy St. Hilaire, Pessac, France (T.D.), Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (M.L.-J., P. Ø.E

Knappskog, Stian; Department of Biomedicine, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., T.T., K.V., J.A.H., J.V.J., R.J., H.S.S., L.L., T.D., P.Ø.E., R.B., H.M.), KG Jebsen Brain Tumor Research Center, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., K.V., J.A.H., J.V.J., T.D., P. Ø.E., S.P.N., R.B., H.M.), Department of Clinical Science, University of Bergen, Norway (S.K.), Department of Oncology, Haukeland University Hospital, Bergen, Norway (S.K.), Norlux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (O.K., S.F., S.P.N., R.B.), Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK (A.S.), Department of Clinical Pharmacy, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany (S.F., C.A.R.), Department of Neurooncology, University Hospital Heidelberg, Germany (G.S., F.W.), Institute of Scientific Instruments, ASCR, Brno, Czech Republic (R.J.), Edinger-Intsitute, Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H.), Department of Pathology, Haukeland University Hospital, Bergen, Norway (J.A.H., H.M.), Department of Clinical Neurosciences, University of Cambridge, UK (S.G.P., C.W.), Statistics and Computational Biology Laboratory, University of Cambridge, UK (I.S.), Neuro Clinic, Haukeland University Hospital, Bergen, Norway, Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Germany (P.E.), Department of Systems Medicine, University of Rome «Tor Vergata», Rome, Italy (G.G.), INSERM U1029 - University of Bordeaux, Allée Geoffroy St. Hilaire, Pessac, France (T.D.), Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (M.L.-J., P. Ø.E

Keunen, Olivier; Department of Biomedicine, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., T.T., K.V., J.A.H., J.V.J., R.J., H.S.S., L.L., T.D., P.Ø.E., R.B., H.M.), KG Jebsen Brain Tumor Research Center, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., K.V., J.A.H., J.V.J., T.D., P. Ø.E., S.P.N., R.B., H.M.), Department of Clinical Science, University of Bergen, Norway (S.K.), Department of Oncology, Haukeland University Hospital, Bergen, Norway (S.K.), Norlux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (O.K., S.F., S.P.N., R.B.), Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK (A.S.), Department of Clinical Pharmacy, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany (S.F., C.A.R.), Department of Neurooncology, University Hospital Heidelberg, Germany (G.S., F.W.), Institute of Scientific Instruments, ASCR, Brno, Czech Republic (R.J.), Edinger-Intsitute, Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H.), Department of Pathology, Haukeland University Hospital, Bergen, Norway (J.A.H., H.M.), Department of Clinical Neurosciences, University of Cambridge, UK (S.G.P., C.W.), Statistics and Computational Biology Laboratory, University of Cambridge, UK (I.S.), Neuro Clinic, Haukeland University Hospital, Bergen, Norway, Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Germany (P.E.), Department of Systems Medicine, University of Rome «Tor Vergata», Rome, Italy (G.G.), INSERM U1029 - University of Bordeaux, Allée Geoffroy St. Hilaire, Pessac, France (T.D.), Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (M.L.-J., P. Ø.E

Sottoriva, Andrea; Department of Biomedicine, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., T.T., K.V., J.A.H., J.V.J., R.J., H.S.S., L.L., T.D., P.Ø.E., R.B., H.M.), KG Jebsen Brain Tumor Research Center, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., K.V., J.A.H., J.V.J., T.D., P. Ø.E., S.P.N., R.B., H.M.), Department of Clinical Science, University of Bergen, Norway (S.K.), Department of Oncology, Haukeland University Hospital, Bergen, Norway (S.K.), Norlux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (O.K., S.F., S.P.N., R.B.), Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK (A.S.), Department of Clinical Pharmacy, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany (S.F., C.A.R.), Department of Neurooncology, University Hospital Heidelberg, Germany (G.S., F.W.), Institute of Scientific Instruments, ASCR, Brno, Czech Republic (R.J.), Edinger-Intsitute, Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H.), Department of Pathology, Haukeland University Hospital, Bergen, Norway (J.A.H., H.M.), Department of Clinical Neurosciences, University of Cambridge, UK (S.G.P., C.W.), Statistics and Computational Biology Laboratory, University of Cambridge, UK (I.S.), Neuro Clinic, Haukeland University Hospital, Bergen, Norway, Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Germany (P.E.), Department of Systems Medicine, University of Rome «Tor Vergata», Rome, Italy (G.G.), INSERM U1029 - University of Bordeaux, Allée Geoffroy St. Hilaire, Pessac, France (T.D.), Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (M.L.-J., P. Ø.E

Foerster, Sarah; Department of Biomedicine, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., T.T., K.V., J.A.H., J.V.J., R.J., H.S.S., L.L., T.D., P.Ø.E., R.B., H.M.), KG Jebsen Brain Tumor Research Center, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., K.V., J.A.H., J.V.J., T.D., P. Ø.E., S.P.N., R.B., H.M.), Department of Clinical Science, University of Bergen, Norway (S.K.), Department of Oncology, Haukeland University Hospital, Bergen, Norway (S.K.), Norlux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (O.K., S.F., S.P.N., R.B.), Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK (A.S.), Department of Clinical Pharmacy, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany (S.F., C.A.R.), Department of Neurooncology, University Hospital Heidelberg, Germany (G.S., F.W.), Institute of Scientific Instruments, ASCR, Brno, Czech Republic (R.J.), Edinger-Intsitute, Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H.), Department of Pathology, Haukeland University Hospital, Bergen, Norway (J.A.H., H.M.), Department of Clinical Neurosciences, University of Cambridge, UK (S.G.P., C.W.), Statistics and Computational Biology Laboratory, University of Cambridge, UK (I.S.), Neuro Clinic, Haukeland University Hospital, Bergen, Norway, Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Germany (P.E.), Department of Systems Medicine, University of Rome «Tor Vergata», Rome, Italy (G.G.), INSERM U1029 - University of Bordeaux, Allée Geoffroy St. Hilaire, Pessac, France (T.D.), Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (M.L.-J., P. Ø.E

Solecki, Gergely; Department of Biomedicine, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., T.T., K.V., J.A.H., J.V.J., R.J., H.S.S., L.L., T.D., P.Ø.E., R.B., H.M.), KG Jebsen Brain Tumor Research Center, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., K.V., J.A.H., J.V.J., T.D., P. Ø.E., S.P.N., R.B., H.M.), Department of Clinical Science, University of Bergen, Norway (S.K.), Department of Oncology, Haukeland University Hospital, Bergen, Norway (S.K.), Norlux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (O.K., S.F., S.P.N., R.B.), Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK (A.S.), Department of Clinical Pharmacy, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany (S.F., C.A.R.), Department of Neurooncology, University Hospital Heidelberg, Germany (G.S., F.W.), Institute of Scientific Instruments, ASCR, Brno, Czech Republic (R.J.), Edinger-Intsitute, Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H.), Department of Pathology, Haukeland University Hospital, Bergen, Norway (J.A.H., H.M.), Department of Clinical Neurosciences, University of Cambridge, UK (S.G.P., C.W.), Statistics and Computational Biology Laboratory, University of Cambridge, UK (I.S.), Neuro Clinic, Haukeland University Hospital, Bergen, Norway, Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Germany (P.E.), Department of Systems Medicine, University of Rome «Tor Vergata», Rome, Italy (G.G.), INSERM U1029 - University of Bordeaux, Allée Geoffroy St. Hilaire, Pessac, France (T.D.), Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (M.L.-J., P. Ø.E

Taxt, Torfinn; Department of Biomedicine, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., T.T., K.V., J.A.H., J.V.J., R.J., H.S.S., L.L., T.D., P.Ø.E., R.B., H.M.), KG Jebsen Brain Tumor Research Center, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., K.V., J.A.H., J.V.J., T.D., P. Ø.E., S.P.N., R.B., H.M.), Department of Clinical Science, University of Bergen, Norway (S.K.), Department of Oncology, Haukeland University Hospital, Bergen, Norway (S.K.), Norlux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (O.K., S.F., S.P.N., R.B.), Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK (A.S.), Department of Clinical Pharmacy, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany (S.F., C.A.R.), Department of Neurooncology, University Hospital Heidelberg, Germany (G.S., F.W.), Institute of Scientific Instruments, ASCR, Brno, Czech Republic (R.J.), Edinger-Intsitute, Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H.), Department of Pathology, Haukeland University Hospital, Bergen, Norway (J.A.H., H.M.), Department of Clinical Neurosciences, University of Cambridge, UK (S.G.P., C.W.), Statistics and Computational Biology Laboratory, University of Cambridge, UK (I.S.), Neuro Clinic, Haukeland University Hospital, Bergen, Norway, Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Germany (P.E.), Department of Systems Medicine, University of Rome «Tor Vergata», Rome, Italy (G.G.), INSERM U1029 - University of Bordeaux, Allée Geoffroy St. Hilaire, Pessac, France (T.D.), Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (M.L.-J., P. Ø.E

Jirik, Radovan; Department of Biomedicine, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., T.T., K.V., J.A.H., J.V.J., R.J., H.S.S., L.L., T.D., P.Ø.E., R.B., H.M.), KG Jebsen Brain Tumor Research Center, University of Bergen, Norway (E.E., G.V.R., K.M.T., O.K., K.V., J.A.H., J.V.J., T.D., P. Ø.E., S.P.N., R.B., H.M.), Department of Clinical Science, University of Bergen, Norway (S.K.), Department of Oncology, Haukeland University Hospital, Bergen, Norway (S.K.), Norlux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg (O.K., S.F., S.P.N., R.B.), Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK (A.S.), Department of Clinical Pharmacy, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany (S.F., C.A.R.), Department of Neurooncology, University Hospital Heidelberg, Germany (G.S., F.W.), Institute of Scientific Instruments, ASCR, Brno, Czech Republic (R.J.), Edinger-Intsitute, Goethe-University Medical School, Frankfurt am Main, Germany (P.N.H.), Department of Pathology, Haukeland University Hospital, Bergen, Norway (J.A.H., H.M.), Department of Clinical Neurosciences, University of Cambridge, UK (S.G.P., C.W.), Statistics and Computational Biology Laboratory, University of Cambridge, UK (I.S.), Neuro Clinic, Haukeland University Hospital, Bergen, Norway, Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Germany (P.E.), Department of Systems Medicine, University of Rome «Tor Vergata», Rome, Italy (G.G.), INSERM U1029 - University of Bordeaux, Allée Geoffroy St. Hilaire, Pessac, France (T.D.), Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway (M.L.-J., P. Ø.E

Plus d'auteurs (21 en +)

Co-auteurs externes :

yes

Langue du document :

Anglais

Titre :

EGFRvIII mutations can emerge as late and heterogenous events in glioblastoma development and promote angiogenesis through Src activation.

Date de publication/diffusion :

décembre 2016

Titre du périodique :

Neuro-Oncology

ISSN :

1522-8517

eISSN :

1523-5866

Maison d'édition :

Oxford University Press, England

Volume/Tome :

Fascicule/Saison :

Pagination :

1644 - 1655

Peer reviewed :

Peer reviewed vérifié par ORBi

URL complémentaire :

http://academic.oup.com/neuro-oncology/article-pdf/18/12/1644/8328326/now113.pdf

Organisme subsidiant :

Research Council of Norway, The Norwegian Cancer Society, Helse Vest, Haukeland University Hospital
Research Foundation, the Bergen Medical Research Foundation
Italian Association for Cancer Research
Ministry of Education, Youth, and Sports of the Czech Republic

Disponible sur ORBilu :

depuis le 16 février 2024

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