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dc.contributor.author | Krusche, Benjamin | |
dc.contributor.author | Ottone, Cristina | |
dc.contributor.author | Clements, Melanie P | |
dc.contributor.author | Johnstone, Ewan R | |
dc.contributor.author | Goetsch, Katrin | |
dc.contributor.author | Lieven, Huang | |
dc.contributor.author | Mota, Silvia G | |
dc.contributor.author | Singh, Poonam | |
dc.contributor.author | Khadayate, Sanjay | |
dc.contributor.author | Ashraf, Azhaar | |
dc.contributor.author | Davies, Timothy | |
dc.contributor.author | Pollard, Steven M | |
dc.contributor.author | De Paola, Vincenzo | |
dc.contributor.author | Roncaroli, Federico | |
dc.contributor.author | Martinez Torrecuadrada, Jorge Luis | |
dc.contributor.author | Bertone, Paul | |
dc.contributor.author | Parrinello, Simona | |
dc.date.accessioned | 2019-07-11T08:06:07Z | |
dc.date.available | 2019-07-11T08:06:07Z | |
dc.date.issued | 2016-06-28 | |
dc.identifier.citation | Elife. 2016;5. pii: e14845. | es_ES |
dc.identifier.issn | 2050-084X | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/7888 | |
dc.description.abstract | Glioblastomas (GBM) are aggressive and therapy-resistant brain tumours, which contain a subpopulation of tumour-propagating glioblastoma stem-like cells (GSC) thought to drive progression and recurrence. Diffuse invasion of the brain parenchyma, including along preexisting blood vessels, is a leading cause of therapeutic resistance, but the mechanisms remain unclear. Here, we show that ephrin-B2 mediates GSC perivascular invasion. Intravital imaging, coupled with mechanistic studies in murine GBM models and patient-derived GSC, revealed that endothelial ephrin-B2 compartmentalises non-tumourigenic cells. In contrast, upregulation of the same ephrin-B2 ligand in GSC enabled perivascular migration through homotypic forward signalling. Surprisingly, ephrin-B2 reverse signalling also promoted tumourigenesis cell-autonomously, by mediating anchorage-independent cytokinesis via RhoA. In human GSC-derived orthotopic xenografts, EFNB2 knock-down blocked tumour initiation and treatment of established tumours with ephrin-B2-blocking antibodies suppressed progression. Thus, our results indicate that targeting ephrin-B2 may be an effective strategy for the simultaneous inhibition of invasion and proliferation in GBM. | es_ES |
dc.description.sponsorship | this work was funded by the Medical Research Council, UK (CO, BK, MPC, KG, SK, AA, TD and SP), the Royal Society (SP) and the Regional Government of Madrid/European Social Fund (JLM-T) We thank A Uren and C Jorgensen for critical reading of the manuscript, A Lloyd, A Ridley, E Batlle, H Augustin and M Herlyn for constructs and A. Lloyd for NF1fl/fl brain tissue. We are also grateful to the Imperial College Healthcare Tissue Bank for supplying the human glioblastoma samples and to the patients who donated their tissue for research. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | eLife Sciences Publications | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | Eph/ephrin | es_ES |
dc.subject | GBM | es_ES |
dc.subject | Cancer biology | es_ES |
dc.subject | Cancer stem cells | es_ES |
dc.subject | Cell biology | es_ES |
dc.subject | Human | es_ES |
dc.subject | Nouse | es_ES |
dc.subject | Perivascular invasion | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Ephrin-B2 | es_ES |
dc.subject.mesh | Glioblastoma | es_ES |
dc.subject.mesh | Heterografts | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Intravital Microscopy | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Neoplastic Stem Cells | es_ES |
dc.subject.mesh | Cell Movement | es_ES |
dc.subject.mesh | Cell Proliferation | es_ES |
dc.title | EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 27350048 | es_ES |
dc.format.volume | 5 | es_ES |
dc.identifier.doi | 10.7554/eLife.14845 | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Medical Research Council Cell Interactions and Cancer | |
dc.contributor.funder | Royal Society (Reino Unido) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2050-084X | es_ES |
dc.relation.publisherversion | https://doi.org/10.7554/eLife.14845. | es_ES |
dc.identifier.journal | eLife | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Unidades técnicas::Unidad de Cristalografía e Ingeniería de Proteínas | es_ES |
dc.rights.accessRights | open access | es_ES |