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dc.contributor.authorLee, B. Y.
dc.contributor.authorHogg, E. K. J.
dc.contributor.authorBelow, C. R.
dc.contributor.authorKononov, A.
dc.contributor.authorBlanco-Gomez, A.
dc.contributor.authorHeider, F.
dc.contributor.authorXu, J.
dc.contributor.authorHutton, C.
dc.contributor.authorZhang, X.
dc.contributor.authorScheidt, T.
dc.contributor.authorBeattie, K.
dc.contributor.authorLamarca, Angela
dc.contributor.authorMcNamara, Mairéad G
dc.contributor.authorValle, Juan W
dc.contributor.authorJørgensen, Claus
dc.date.accessioned2022-01-31T15:43:50Z
dc.date.available2022-01-31T15:43:50Z
dc.date.issued2021en
dc.identifier.citationLee BY, Hogg EKJ, Below CR, Kononov A, Blanco-Gomez A, Heider F, et al. Heterocellular OSM-OSMR signalling reprograms fibroblasts to promote pancreatic cancer growth and metastasis. Nature Communications. 2021;12(1):20.en
dc.identifier.pmid34921158en
dc.identifier.doi10.1038/s41467-021-27607-8en
dc.identifier.urihttp://hdl.handle.net/10541/625000
dc.description.abstractPancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with a complex microenvironment. Dichotomous tumour-promoting and -restrictive roles have been ascribed to the tumour microenvironment, however the effects of individual stromal subsets remain incompletely characterised. Here, we describe how heterocellular Oncostatin M (OSM) - Oncostatin M Receptor (OSMR) signalling reprograms fibroblasts, regulates tumour growth and metastasis. Macrophage-secreted OSM stimulates inflammatory gene expression in cancer-associated fibroblasts (CAFs), which in turn induce a pro-tumourigenic environment and engage tumour cell survival and migratory signalling pathways. Tumour cells implanted in Osm-deficient (Osm−/−) mice display an epithelial-dominated morphology, reduced tumour growth and do not metastasise. Moreover, the tumour microenvironment of Osm−/− animals exhibit increased abundance of α smooth muscle actin positive myofibroblasts and a shift in myeloid and T cell phenotypes, consistent with a more immunogenic environment. Taken together, these data demonstrate how OSM-OSMR signalling coordinates heterocellular interactions to drive a pro-tumourigenic environment in PDA.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1038/s41467-021-27607-8en
dc.titleHeterocellular OSM-OSMR signalling reprograms fibroblasts to promote pancreatic cancer growth and metastasisen
dc.typeArticleen
dc.contributor.departmentCancer Research UK Manchester Institute, The University of Manchester, Alderley Park, SK10 4TG Manchester, UKen
dc.identifier.journalNature Communicationsen
dc.description.noteen]
refterms.dateFOA2022-04-20T11:50:46Z


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