Imperial College London
Alternate

ProfessorRobertGlen

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Computational Medicine
 
 
 
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Contact

 

+44 (0)20 7594 7912r.glen Website

 
 
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Location

 

362Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Harford-Wright:2017:brain/awx253,
author = {Harford-Wright, E and Andre-Gregoire, G and Jacobs, KA and Treps, L and Le, Gonidec S and Leclair, HM and Gonzalez-Diest, S and Roux, Q and Guillonneau, F and Loussouarn, D and Oliver, L and Vallette, FM and Foufelle, F and Valet, P and Davenport, AP and Glen, RC and Bidere, N and Gavard, J},
doi = {brain/awx253},
journal = {Brain},
pages = {2939--2954},
title = {Pharmacological targeting of apelin impairs glioblastoma growth},
url = {http://dx.doi.org/10.1093/brain/awx253},
volume = {140},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Glioblastoma are highly aggressive brain tumours that are associated with an extremely poor prognosis. Within these tumours exists a subpopulation of highly plastic self-renewing cancer cells that retain the ability to expand ex vivo as tumourspheres, induce tumour growth in mice, and have been implicated in radio- and chemo-resistance. Although their identity and fate are regulated by external cues emanating from endothelial cells, the nature of such signals remains unknown. Here, we used a mass spectrometry proteomic approach to characterize the factors released by brain endothelial cells. We report the identification of the vasoactive peptide apelin as a central regulator for endothelial-mediated maintenance of glioblastoma patient-derived cells with stem-like properties. Genetic and pharmacological targeting of apelin cognate receptor abrogates apelin- and endothelial-mediated expansion of glioblastoma patient-derived cells with stem-like properties in vitro and suppresses tumour growth in vivo. Functionally, selective competitive antagonists of apelin receptor were shown to be safe and effective in reducing tumour expansion and lengthening the survival of intracranially xenografted mice. Therefore, the apelin/apelin receptor signalling nexus may operate as a paracrine signal that sustains tumour cell expansion and progression, suggesting that apelin is a druggable factor in glioblastoma.
AU  - Harford-Wright,E
AU  - Andre-Gregoire,G
AU  - Jacobs,KA
AU  - Treps,L
AU  - Le,Gonidec S
AU  - Leclair,HM
AU  - Gonzalez-Diest,S
AU  - Roux,Q
AU  - Guillonneau,F
AU  - Loussouarn,D
AU  - Oliver,L
AU  - Vallette,FM
AU  - Foufelle,F
AU  - Valet,P
AU  - Davenport,AP
AU  - Glen,RC
AU  - Bidere,N
AU  - Gavard,J
DO  - brain/awx253
EP  - 2954
PY  - 2017///
SN  - 1460-2156
SP  - 2939
TI  - Pharmacological targeting of apelin impairs glioblastoma growth
T2  - Brain
UR  - http://dx.doi.org/10.1093/brain/awx253
UR  - http://hdl.handle.net/10044/1/52493
VL  - 140
ER  -
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