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dc.contributor.authorKrusche, Benjamin
dc.contributor.authorOttone, Cristina
dc.contributor.authorClements, Melanie P
dc.contributor.authorJohnstone, Ewan R
dc.contributor.authorGoetsch, Katrin
dc.contributor.authorLieven, Huang
dc.contributor.authorMota, Silvia G
dc.contributor.authorSingh, Poonam
dc.contributor.authorKhadayate, Sanjay
dc.contributor.authorAshraf, Azhaar
dc.contributor.authorDavies, Timothy
dc.contributor.authorPollard, Steven M
dc.contributor.authorDe Paola, Vincenzo
dc.contributor.authorRoncaroli, Federico
dc.contributor.authorMartinez Torrecuadrada, Jorge Luis 
dc.contributor.authorBertone, Paul
dc.contributor.authorParrinello, Simona
dc.date.accessioned2019-07-11T08:06:07Z
dc.date.available2019-07-11T08:06:07Z
dc.date.issued2016-06-28
dc.identifier.citationElife. 2016;5. pii: e14845.es_ES
dc.identifier.issn2050-084Xes_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7888
dc.description.abstractGlioblastomas (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.sponsorshipthis 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.isoenges_ES
dc.publishereLife Sciences Publications es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectEph/ephrines_ES
dc.subjectGBMes_ES
dc.subjectCancer biologyes_ES
dc.subjectCancer stem cellses_ES
dc.subjectCell biologyes_ES
dc.subjectHumanes_ES
dc.subjectNousees_ES
dc.subjectPerivascular invasiones_ES
dc.subject.meshAnimals es_ES
dc.subject.meshEphrin-B2 es_ES
dc.subject.meshGlioblastoma es_ES
dc.subject.meshHeterografts es_ES
dc.subject.meshHumans es_ES
dc.subject.meshIntravital Microscopy es_ES
dc.subject.meshMice es_ES
dc.subject.meshNeoplastic Stem Cells es_ES
dc.subject.meshCell Movement es_ES
dc.subject.meshCell Proliferation es_ES
dc.titleEphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cellses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID27350048es_ES
dc.format.volume5es_ES
dc.identifier.doi10.7554/eLife.14845es_ES
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderMedical Research Council Cell Interactions and Cancer
dc.contributor.funderRoyal Society (Reino Unido) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2050-084Xes_ES
dc.relation.publisherversionhttps://doi.org/10.7554/eLife.14845.es_ES
dc.identifier.journaleLifees_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Cristalografía e Ingeniería de Proteínases_ES
dc.rights.accessRightsopen accesses_ES


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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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