Imperial College London
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Vincenzo De Paola

Faculty of Medicine, Department of Brain Sciences

Reader in Translational Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 2501vincenzo.depaola Website CV

 
 
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Assistant

 

Miss Lydia Lawson +44 (0)20 7594 1264

 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Krusche:2016:10.7554/eLife.14845,
author = {Krusche, B and Ottone, C and Clements, MP and Johnstone, E and Goetsch, K and Huang, L and Mota, SG and Singh, P and Khadayate, S and Ashraf, T and Davies, T and Pollard, SM and De, Paola V and Roncaroli, F and Torrecuadrada, JM and Bertone, P and Parrinello, S},
doi = {10.7554/eLife.14845},
journal = {eLife},
title = {EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells},
url = {http://dx.doi.org/10.7554/eLife.14845},
volume = {5},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Krusche,B
AU  - Ottone,C
AU  - Clements,MP
AU  - Johnstone,E
AU  - Goetsch,K
AU  - Huang,L
AU  - Mota,SG
AU  - Singh,P
AU  - Khadayate,S
AU  - Ashraf,T
AU  - Davies,T
AU  - Pollard,SM
AU  - De,Paola V
AU  - Roncaroli,F
AU  - Torrecuadrada,JM
AU  - Bertone,P
AU  - Parrinello,S
DO  - 10.7554/eLife.14845
PY  - 2016///
SN  - 2050-084X
TI  - EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells
T2  - eLife
UR  - http://dx.doi.org/10.7554/eLife.14845
UR  - http://hdl.handle.net/10044/1/34450
VL  - 5
ER  -
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