Heterocellular OSM-OSMR signalling reprograms fibroblasts to promote pancreatic cancer growth and metastasis
Authors
Lee, B. Y.Hogg, E. K. J.
Below, C. R.
Kononov, A.
Blanco-Gomez, A.
Heider, F.
Xu, J.
Hutton, C.
Zhang, X.
Scheidt, T.
Beattie, K.
Lamarca, Angela
McNamara, Mairéad G
Valle, Juan W
Jørgensen, Claus
Affiliation
Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, SK10 4TG Manchester, UKIssue Date
2021
Metadata
Show full item recordAbstract
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.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.Journal
Nature CommunicationsDOI
10.1038/s41467-021-27607-8PubMed ID
34921158Additional Links
https://dx.doi.org/10.1038/s41467-021-27607-8Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41467-021-27607-8
Scopus Count
Collections
Related articles
- Potent EMT and CSC Phenotypes Are Induced By Oncostatin-M in Pancreatic Cancer.
- Authors: Smigiel JM, Parameswaran N, Jackson MW
- Issue date: 2017 Apr
- Oncostatin M acting via OSMR, augments the actions of IL-1 and TNF in synovial fibroblasts.
- Authors: Le Goff B, Singbrant S, Tonkin BA, Martin TJ, Romas E, Sims NA, Walsh NC
- Issue date: 2014 Aug
- Cancer-associated fibroblasts promote M2 polarization of macrophages in pancreatic ductal adenocarcinoma.
- Authors: Zhang A, Qian Y, Ye Z, Chen H, Xie H, Zhou L, Shen Y, Zheng S
- Issue date: 2017 Feb
- GPR68, a proton-sensing GPCR, mediates interaction of cancer-associated fibroblasts and cancer cells.
- Authors: Wiley SZ, Sriram K, Liang W, Chang SE, French R, McCann T, Sicklick J, Nishihara H, Lowy AM, Insel PA
- Issue date: 2018 Mar
- Integrin α11 in pancreatic stellate cells regulates tumor stroma interaction in pancreatic cancer.
- Authors: Schnittert J, Bansal R, Mardhian DF, van Baarlen J, Östman A, Prakash J
- Issue date: 2019 May