Heterocellular OSM-OSMR signalling reprograms fibroblasts to promote pancreatic cancer growth and metastasis
dc.contributor.author | Lee, B. Y. | |
dc.contributor.author | Hogg, E. K. J. | |
dc.contributor.author | Below, C. R. | |
dc.contributor.author | Kononov, A. | |
dc.contributor.author | Blanco-Gomez, A. | |
dc.contributor.author | Heider, F. | |
dc.contributor.author | Xu, J. | |
dc.contributor.author | Hutton, C. | |
dc.contributor.author | Zhang, X. | |
dc.contributor.author | Scheidt, T. | |
dc.contributor.author | Beattie, K. | |
dc.contributor.author | Lamarca, Angela | |
dc.contributor.author | McNamara, Mairéad G | |
dc.contributor.author | Valle, Juan W | |
dc.contributor.author | Jørgensen, Claus | |
dc.date.accessioned | 2022-01-31T15:43:50Z | |
dc.date.available | 2022-01-31T15:43:50Z | |
dc.date.issued | 2021 | en |
dc.identifier.citation | Lee 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.pmid | 34921158 | en |
dc.identifier.doi | 10.1038/s41467-021-27607-8 | en |
dc.identifier.uri | http://hdl.handle.net/10541/625000 | |
dc.description.abstract | Pancreatic 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.iso | en | en |
dc.relation.url | https://dx.doi.org/10.1038/s41467-021-27607-8 | en |
dc.title | Heterocellular OSM-OSMR signalling reprograms fibroblasts to promote pancreatic cancer growth and metastasis | en |
dc.type | Article | en |
dc.contributor.department | Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, SK10 4TG Manchester, UK | en |
dc.identifier.journal | Nature Communications | en |
dc.description.note | en] | |
refterms.dateFOA | 2022-04-20T11:50:46Z |