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dc.contributor.authorEvans, R
dc.contributor.authorFlores-Borja, F
dc.contributor.authorNassiri, S
dc.contributor.authorMiranda, E
dc.contributor.authorLawler, K
dc.contributor.authorGrigoriadis, A
dc.contributor.authorMonypenny, J
dc.contributor.authorGillet, C
dc.contributor.authorOwen, J
dc.contributor.authorGordon, P
dc.contributor.authorMale, V
dc.contributor.authorCheung, A
dc.contributor.authorNoor, F
dc.contributor.authorBarber, P
dc.contributor.authorMarlow, R
dc.contributor.authorFrancesch-Domenech, E
dc.contributor.authorFruhwirth, G
dc.contributor.authorSquadrito, M
dc.contributor.authorVojnovic, B
dc.contributor.authorTutt, A
dc.contributor.authorFesty, F
dc.contributor.authorDe Palma, M
dc.contributor.authorNg, T
dc.date.accessioned2020-06-08T14:32:35Z
dc.date.issued2019-05
dc.identifier.citationCell reports, 2019, 27 (7), pp. 1967 - 1978.e4
dc.identifier.issn2211-1247
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3698
dc.identifier.eissn2211-1247
dc.identifier.doi10.1016/j.celrep.2019.04.076
dc.description.abstractLymphatic 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.formatPrint
dc.format.extent1967 - 1978.e4
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectMacrophages
dc.subjectEndothelial Cells
dc.subjectLymphatic Vessels
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectMice, Inbred C57BL
dc.subjectHumans
dc.subjectMice
dc.subjectLymphatic Metastasis
dc.subjectrhoA GTP-Binding Protein
dc.subjectCell Adhesion Molecules
dc.subjectIntegrin beta4
dc.subjectCell Adhesion
dc.subjectSignal Transduction
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectFemale
dc.subjectTransforming Growth Factor beta1
dc.subjectHEK293 Cells
dc.subjectTriple Negative Breast Neoplasms
dc.titleIntegrin-Mediated Macrophage Adhesion Promotes Lymphovascular Dissemination in Breast Cancer.
dc.typeJournal Article
dcterms.dateAccepted2019-04-17
rioxxterms.versionofrecord10.1016/j.celrep.2019.04.076
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell reports
pubs.issue7
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.volume27
pubs.embargo.termsNot known
dc.contributor.icrauthorTutt, Andrewen


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