dc.contributor.author | Evans, R | |
dc.contributor.author | Flores-Borja, F | |
dc.contributor.author | Nassiri, S | |
dc.contributor.author | Miranda, E | |
dc.contributor.author | Lawler, K | |
dc.contributor.author | Grigoriadis, A | |
dc.contributor.author | Monypenny, J | |
dc.contributor.author | Gillet, C | |
dc.contributor.author | Owen, J | |
dc.contributor.author | Gordon, P | |
dc.contributor.author | Male, V | |
dc.contributor.author | Cheung, A | |
dc.contributor.author | Noor, F | |
dc.contributor.author | Barber, P | |
dc.contributor.author | Marlow, R | |
dc.contributor.author | Francesch-Domenech, E | |
dc.contributor.author | Fruhwirth, G | |
dc.contributor.author | Squadrito, M | |
dc.contributor.author | Vojnovic, B | |
dc.contributor.author | Tutt, A | |
dc.contributor.author | Festy, F | |
dc.contributor.author | De Palma, M | |
dc.contributor.author | Ng, T | |
dc.date.accessioned | 2020-06-08T14:32:35Z | |
dc.date.issued | 2019-05-14 | |
dc.identifier.citation | Cell reports, 2019, 27 (7), pp. 1967 - 1978.e4 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3698 | |
dc.identifier.eissn | 2211-1247 | |
dc.identifier.doi | 10.1016/j.celrep.2019.04.076 | |
dc.description.abstract | 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. | |
dc.format | Print | |
dc.format.extent | 1967 - 1978.e4 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Macrophages | |
dc.subject | Endothelial Cells | |
dc.subject | Lymphatic Vessels | |
dc.subject | Animals | |
dc.subject | Mice, Inbred BALB C | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Lymphatic Metastasis | |
dc.subject | rhoA GTP-Binding Protein | |
dc.subject | Cell Adhesion Molecules | |
dc.subject | Integrin beta4 | |
dc.subject | Cell Adhesion | |
dc.subject | Signal Transduction | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Female | |
dc.subject | Transforming Growth Factor beta1 | |
dc.subject | HEK293 Cells | |
dc.subject | Triple Negative Breast Neoplasms | |
dc.title | Integrin-Mediated Macrophage Adhesion Promotes Lymphovascular Dissemination in Breast Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-04-17 | |
rioxxterms.versionofrecord | 10.1016/j.celrep.2019.04.076 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-05 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell reports | |
pubs.issue | 7 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR | |
pubs.publication-status | Published | |
pubs.volume | 27 | |
pubs.embargo.terms | Not known | |
dc.contributor.icrauthor | Tutt, Andrew | |