Dataset Information

Heterocellular OSM-OSMR signalling drives pancreatic tumour growth and metastasis through functional fibroblast reprogramming

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy characterised by a pathologicalfibroinflammatorymicroenvironment. Dichotomous tumour-promoting and -restrictive roles have been ascribed to the tumour microenvironment, however thedisparate effect of individual stromal subsets remains incompletely characterised. Here, we describe how heterocellular OSM-OSMR signalling instructsfibroblast reprogramming,tumourgrowth and metastasis.Macrophage-secreted OSM stimulatesinflammatory gene expression in cancer-associated fibroblasts (CAFs), which in turn induce a pro-tumorigenic environment and engage tumour cellsurvival and migratory signalling pathways. Tumour cells implanted in Osm-deficient (Osm-/-) mice display an epithelial-dominated morphology, reduced tumour growth and did notmetastasise. Moreover, the tumour microenvironment of Osm-/-animals exhibit increased abundance of αSMAposmyofibroblasts 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-tumorigenic environment in PDA.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Pancreas

DISEASE(S): Pancreatic Ductal Carcinoma

SUBMITTER: Brian Lee

LAB HEAD: Claus Jorgensen

PROVIDER: PXD022484 | Pride | 2021-11-29

REPOSITORIES: Pride

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

Lee Brian Y BY Hogg Elizabeth K J EKJ Below Christopher R CR Kononov Alexander A Blanco-Gomez Adrian A Heider Felix F Xu Jingshu J Hutton Colin C Zhang Xiaohong X Scheidt Tamara T Beattie Kenneth K Lamarca Angela A McNamara Mairéad M Valle Juan W JW Jørgensen Claus C

Nature communications 20211217 1

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 ex ...[more]

PMID: 34921158

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	BL_SetA.msf	Msf
	BL_SetA_10_1.raw	Raw
	BL_SetA_10_2.raw	Raw
	BL_SetA_1_1.raw	Raw
	BL_SetA_1_2.raw	Raw