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dc.contributor.authorJungwirth, U
dc.contributor.authorvan Weverwijk, A
dc.contributor.authorEvans, RJ
dc.contributor.authorJenkins, L
dc.contributor.authorVicente, D
dc.contributor.authorAlexander, J
dc.contributor.authorGao, Q
dc.contributor.authorHaider, S
dc.contributor.authorIravani, M
dc.contributor.authorIsacke, CM
dc.date.accessioned2021-08-12T11:06:06Z
dc.date.available2021-08-12T11:06:06Z
dc.date.issued2021-06-10
dc.identifier.citationNature communications, 2021, 12 (1), pp. 3516 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4751
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-021-23583-1
dc.description.abstractProfiling studies have revealed considerable phenotypic heterogeneity in cancer-associated fibroblasts (CAFs) present within the tumour microenvironment, however, functional characterisation of different CAF subsets is hampered by the lack of specific markers defining these populations. Here we show that genetic deletion of the Endo180 (MRC2) receptor, predominantly expressed by a population of matrix-remodelling CAFs, profoundly limits tumour growth and metastasis; effects that can be recapitulated in 3D co-culture assays. This impairment results from a CAF-intrinsic contractility defect and reduced CAF viability, which coupled with the lack of phenotype in the normal mouse, demonstrates that upregulated Endo180 expression by a specific, potentially targetable CAF subset is required to generate a supportive tumour microenvironment. Further, characterisation of a tumour subline selected via serial in vivo passage for its ability to overcome these stromal defects provides important insight into, how tumour cells adapt to a non-activated stroma in the early stages of metastatic colonisation.
dc.formatElectronic
dc.format.extent3516 - ?
dc.languageeng
dc.language.isoeng
dc.publisherNATURE PORTFOLIO
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCells, Cultured
dc.subjectNIH 3T3 Cells
dc.subjectSpheroids, Cellular
dc.subjectExtracellular Matrix
dc.subjectStromal Cells
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectMice, Knockout
dc.subjectHumans
dc.subjectMice
dc.subjectBreast Neoplasms
dc.subjectNeoplasm Metastasis
dc.subjectMembrane Glycoproteins
dc.subjectReceptors, Cell Surface
dc.subjectCoculture Techniques
dc.subjectTumor Stem Cell Assay
dc.subjectCell Proliferation
dc.subjectCell Survival
dc.subjectFemale
dc.subjectTumor Microenvironment
dc.subjectCancer-Associated Fibroblasts
dc.titleImpairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis.
dc.typeJournal Article
dcterms.dateAccepted2021-04-26
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-021-23583-1
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2021-06-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/19/20 Starting Cohort
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/19/20 Starting Cohort
pubs.publication-statusPublished
pubs.volume12
pubs.embargo.termsNot known
icr.researchteamMolecular Cell Biology
icr.researchteamPaediatric Solid Tumour Biology and Therapeutics
icr.researchteamMolecular Cell Biology
icr.researchteamPaediatric Solid Tumour Biology and Therapeutics
dc.contributor.icrauthorEvans, Rachel
dc.contributor.icrauthorGao, Qiong
dc.contributor.icrauthorHaider, Syed
dc.contributor.icrauthorIravani, Marjan
dc.contributor.icrauthorIsacke, Clare


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