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dc.contributor.authorJungwirth, U
dc.contributor.authorvan Weverwijk, A
dc.contributor.authorJenkins, L
dc.contributor.authorAlexander, J
dc.contributor.authorVicente, D
dc.contributor.authorGao, Q
dc.contributor.authorHaider, S
dc.contributor.authorIravani, M
dc.contributor.authorIsacke, CM
dc.date.accessioned2021-12-15T16:06:17Z
dc.date.available2021-12-15T16:06:17Z
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4929
dc.identifier.doi10.1101/2020.05.17.100412
dc.description.abstractAbstract Profiling 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.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleImpairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis
dc.typeJournal Article
dcterms.dateAccepted2021-04-26
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1101/2020.05.17.100412
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.typeJournal Article/Review
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.embargo.termsNot known
icr.researchteamMolecular Cell Biology
dc.contributor.icrauthorIravani, Marjanen_US
dc.contributor.icrauthorIsacke, Clareen_US


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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0