dc.contributor.author | Turrell, FK | |
dc.contributor.author | Orha, R | |
dc.contributor.author | Guppy, NJ | |
dc.contributor.author | Gillespie, A | |
dc.contributor.author | Guelbert, M | |
dc.contributor.author | Starling, C | |
dc.contributor.author | Haider, S | |
dc.contributor.author | Isacke, CM | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2023-06-06T10:39:30Z | |
dc.date.available | 2023-06-06T10:39:30Z | |
dc.date.issued | 2023-04-01 | |
dc.identifier | 10.1038/s43018-023-00525-y | |
dc.identifier.citation | Nature Cancer, 2023, 4 (4), pp. 468 - 484 | |
dc.identifier.issn | 2662-1347 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5829 | |
dc.identifier.eissn | 2662-1347 | |
dc.identifier.eissn | 2662-1347 | |
dc.identifier.doi | 10.1038/s43018-023-00525-y | |
dc.description.abstract | Patients with estrogen receptor (ER)-positive breast cancer are at risk of metastatic relapse for decades after primary tumor resection and treatment, a consequence of dormant disseminated tumor cells (DTCs) reawakening at secondary sites. Here we use syngeneic ER+ mouse models in which DTCs display a dormant phenotype in young mice but accelerated metastatic outgrowth in an aged or fibrotic microenvironment. In young mice, low-level Pdgfc expression by ER+ DTCs is required for their maintenance in secondary sites but is insufficient to support development of macrometastases. By contrast, the platelet-derived growth factor (PDGF)-Chi environment of aging or fibrotic lungs promotes DTC proliferation and upregulates tumor cell Pdgfc expression stimulating further stromal activation, events that can be blocked by pharmacological inhibition of PDGFRα or with a PDGF-C-blocking antibody. These results highlight the role of the changing microenvironment in regulating DTC outgrowth and the opportunity to target PDGF-C signaling to limit metastatic relapse in ER+ breast cancer. | |
dc.format | Print-Electronic | |
dc.format.extent | 468 - 484 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.relation.ispartof | Nature Cancer | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Animals | |
dc.subject | Mice | |
dc.subject | Lymphokines | |
dc.subject | Platelet-Derived Growth Factor | |
dc.subject | Recurrence | |
dc.subject | Tumor Microenvironment | |
dc.subject | Breast Neoplasms | |
dc.title | Age-associated microenvironmental changes highlight the role of PDGF-C in ER+ breast cancer metastatic relapse. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-02-07 | |
dc.date.updated | 2023-06-06T10:38:33Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s43018-023-00525-y | |
rioxxterms.licenseref.startdate | 2023-04-01 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36914817 | |
pubs.issue | 4 | |
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.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1038/s43018-023-00525-y | |
pubs.volume | 4 | |
icr.researchteam | BCR Bioinformatics Group | |
icr.researchteam | Molecular Cell Biology | |
dc.contributor.icrauthor | Guelbert, Matthew | |
dc.contributor.icrauthor | Haider, Syed | |
dc.contributor.icrauthor | Isacke, Clare | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Ros Eeles) on 2023-06-06. Deposit type is initial. No. of files: 1. Files: Age-associated microenvironmental changes highlight the role of PDGF-C in ERsup+sup breast cancer metastatic relapse.pdf | |