2026-06-14T03:33:57Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/78882024-11-29T21:58:05Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Krusche, Benjamin
author
Ottone, Cristina
author
Clements, Melanie P
author
Johnstone, Ewan R
author
Goetsch, Katrin
author
Lieven, Huang
author
Mota, Silvia G
author
Singh, Poonam
author
Khadayate, Sanjay
author
Ashraf, Azhaar
author
Davies, Timothy
author
Pollard, Steven M
author
De Paola, Vincenzo
author
Roncaroli, Federico
author
Martinez Torrecuadrada, Jorge Luis
author
Bertone, Paul
author
Parrinello, Simona
funder
Comunidad de Madrid (España)
funder
Medical Research Council Cell Interactions and Cancer
funder
Royal Society (Reino Unido)
2019-07-11T08:06:07Z
2019-07-11T08:06:07Z
2016-06-28
Elife. 2016;5. pii: e14845.
10.7554/eLife.14845
2050-084X
2050-084X
eLife
27350048
http://hdl.handle.net/20.500.12105/7888
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.
eng
Eph/ephrin
GBM
Cancer biology
Cancer stem cells
Cell biology
Human
Nouse
Perivascular invasion
EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells
journal article
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EphrinB2drivesperivascularinvasion_2016.pdf
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https://repisalud.isciii.es/bitstreams/bdbd7397-d856-413f-ae20-a56f015175b4/download
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EphrinB2drivesperivascularinvasion_2016.pdf.txt