dc.contributor.author | Jungwirth, U | |
dc.contributor.author | van Weverwijk, A | |
dc.contributor.author | Evans, RJ | |
dc.contributor.author | Jenkins, L | |
dc.contributor.author | Vicente, D | |
dc.contributor.author | Alexander, J | |
dc.contributor.author | Gao, Q | |
dc.contributor.author | Haider, S | |
dc.contributor.author | Iravani, M | |
dc.contributor.author | Isacke, CM | |
dc.date.accessioned | 2021-08-12T11:06:06Z | |
dc.date.available | 2021-08-12T11:06:06Z | |
dc.date.issued | 2021-06-10 | |
dc.identifier.citation | Nature communications, 2021, 12 (1), pp. 3516 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4751 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-021-23583-1 | |
dc.description.abstract | 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.format | Electronic | |
dc.format.extent | 3516 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cells, Cultured | |
dc.subject | NIH 3T3 Cells | |
dc.subject | Spheroids, Cellular | |
dc.subject | Extracellular Matrix | |
dc.subject | Stromal Cells | |
dc.subject | Animals | |
dc.subject | Mice, Inbred BALB C | |
dc.subject | Mice, Knockout | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Breast Neoplasms | |
dc.subject | Neoplasm Metastasis | |
dc.subject | Membrane Glycoproteins | |
dc.subject | Receptors, Cell Surface | |
dc.subject | Coculture Techniques | |
dc.subject | Tumor Stem Cell Assay | |
dc.subject | Cell Proliferation | |
dc.subject | Cell Survival | |
dc.subject | Female | |
dc.subject | Tumor Microenvironment | |
dc.subject | Cancer-Associated Fibroblasts | |
dc.title | Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-04-26 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41467-021-23583-1 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-06-10 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.issue | 1 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 12 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Molecular Cell Biology | |
icr.researchteam | Paediatric Solid Tumour Biology and Therapeutics | |
icr.researchteam | Molecular Cell Biology | |
icr.researchteam | Paediatric Solid Tumour Biology and Therapeutics | |
dc.contributor.icrauthor | Evans, Rachel | |
dc.contributor.icrauthor | Gao, Qiong | |
dc.contributor.icrauthor | Haider, Syed | |
dc.contributor.icrauthor | Iravani, Marjan | |
dc.contributor.icrauthor | Isacke, Clare | |