Imperial College London
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DrVictoriaMale

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer in Reproductive Immunology
 
 
 
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v.male

 
 
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Location

 

Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Evans:2019:10.1016/j.celrep.2019.04.076,
author = {Evans, R and Flores-Borja, F and Nassiri, S and Miranda, E and Lawler, K and Grigoriadis, A and Monypenny, J and Gillet, C and Owen, J and Gordon, P and Male, V and Cheung, A and Noor, F and Barber, P and Marlow, R and Francesch-Domenech, E and Fruhwirth, G and Squadrito, M and Vojnovic, B and Tutt, A and Festy, F and De, Palma M and Ng, T},
doi = {10.1016/j.celrep.2019.04.076},
journal = {Cell Reports},
pages = {1967--1978.e4},
title = {Integrin-mediated macrophage adhesion promotes lymphovascular dissemination in breast cancer},
url = {http://dx.doi.org/10.1016/j.celrep.2019.04.076},
volume = {27},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Lymphatic vasculature is crucial for metastasis in triple-negative breast cancer (TNBC); however, cellular and molecular drivers controlling lymphovascular metastasis are poorly understood. We define a macrophage-dependent signaling cascade that facilitates metastasis through lymphovascular remodeling. TNBC cells instigate mRNA changes in macrophages, resulting in β4 integrin-dependent adhesion to the lymphovasculature. β4 integrin retains macrophages proximal to lymphatic endothelial cells (LECs), where release of TGF-β1 drives LEC contraction via RhoA activation. Macrophages promote gross architectural changes to lymphovasculature by increasing dilation, hyperpermeability, and disorganization. TGF-β1 drives β4 integrin clustering at the macrophage plasma membrane, further promoting macrophage adhesion and demonstrating the dual functionality of TGF-β1 signaling in this context. β4 integrin-expressing macrophages were identified in human breast tumors, and a combination of vascular-remodeling macrophage gene signature and TGF-β signaling scores correlates with metastasis. We postulate that future clinical strategies for patients with TNBC should target crosstalk between β4 integrin and TGF-β1.
AU  - Evans,R
AU  - Flores-Borja,F
AU  - Nassiri,S
AU  - Miranda,E
AU  - Lawler,K
AU  - Grigoriadis,A
AU  - Monypenny,J
AU  - Gillet,C
AU  - Owen,J
AU  - Gordon,P
AU  - Male,V
AU  - Cheung,A
AU  - Noor,F
AU  - Barber,P
AU  - Marlow,R
AU  - Francesch-Domenech,E
AU  - Fruhwirth,G
AU  - Squadrito,M
AU  - Vojnovic,B
AU  - Tutt,A
AU  - Festy,F
AU  - De,Palma M
AU  - Ng,T
DO  - 10.1016/j.celrep.2019.04.076
EP  - 1978
PY  - 2019///
SN  - 2211-1247
SP  - 1967
TI  - Integrin-mediated macrophage adhesion promotes lymphovascular dissemination in breast cancer
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2019.04.076
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000467811500003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/70256
VL  - 27
ER  -
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