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Heterocellular OSM-OSMR signalling reprograms fibroblasts to promote pancreatic cancer growth and metastasis.

Nature communications (2021-12-19)
Brian Y Lee, Elizabeth K J Hogg, Christopher R Below, Alexander Kononov, Adrian Blanco-Gomez, Felix Heider, Jingshu Xu, Colin Hutton, Xiaohong Zhang, Tamara Scheidt, Kenneth Beattie, Angela Lamarca, Mairéad McNamara, Juan W Valle, Claus Jørgensen

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.

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Product Description

Anti-Actin, α-Smooth Muscle antibody, Mouse monoclonal, clone 1A4, purified from hybridoma cell culture
Hyaluronidase from bovine testes, Type VIII, lyophilized powder, 300-1,000 U/mg
Accutase® solution, sterile-filtered, suitable for cell culture
DNase I, grade II, from bovine pancreas
Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
Bovine Serum Albumin, heat shock fraction, protease free, pH 7, ≥98%
PTP Assay Kit 1, PTP Assay Kit 1 can be used to detect PTP-1B activity by dephosphorylation of the phosphopeptide (RRLIEDAEpYAARG) using malachite green detection, or by hydrolysis of pNPP.