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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Publications

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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Project description:The honeybee brain is comprised of a nervous system that sufficiently regulates this life transition. Knowledge about how protein phosphorylation functions in regards to the neurobiological activities in the honeybee brain to drive the age-specific labor division is still lacking. Protein phosphorylation, the most common post-translational modification (PTM), is a key switch for rapid on-off control of signaling cascades that regulate cell differentiation and development, enzyme activity and metabolic maintenance in living cells. A fundamental mechanism for regulating signaling network and protein activity is the covalent PTM of serine (Ser), threonine (Thr), and tyrosine (Tyr) residues with phosphate. Fortunately, because of advances in phosphopeptide enrichment and improvements in mass spectrometry (MS) instrumentation and methods, phosphoproteomics has enabled large-scale identification of protein phosphorylation sites and phosphorylation networks in biological samples. Although the proteome has been mapped in the brain of nurse and forager bees, knowledge about age-specific effects of phosphorylation regulation on proteins in the honeybee brain is still lacking. Moreover, information in regards to the honeybee phosphoproteome is also very limited. Only very recently, in-depth phosphoproteomics analyses of protein phosphorylation networks in the hypopharyngealgland of the honeybee have been reported. Although the phosphoproteome analyses during the development of brood and salivary glands has been reported, only very limited proteins were phosphorylated and phosphorylation sites of those phosphoproteins were not assigned. Therefore, a comprehensive characterization of phosphoproteomics and changes in the brains of nurse and forager bees is key to understand the phosphorylation events underlying age-specific physiology to achieve the completion of biological missions in this well-organized social community of the honeybee. Honeybee (A. m. ligustica) colonies used for sampling were raised at the apiary of the Institute of Apicultural Research, Chinese Academy of Agricultural Science, Beijing. Newly emerged (<12 h after emergence) worker bees were marked on their thoraxes and placed back into the colonies to develop and then the marked nurse and forager bees were collected on days 10 and 20, respectively. There were 150 bees sampled from each of the five colonies which have queens at the same age. In brief, for each time point, worker bees were sampled from five colonies, and pooled all samples for further analysis. This procedure was repeated three times, so that we finally ended up with three independent biological replicates per time point, each consisting of 150 honeybees. Then their brains were dissected, and the brain samples were pooled and stored at −80 °C for further analysis. All the colonies were managed with almost identical population, food, and brood during the nectar flow of chaste berry (Vitexnegundo L.) in June.

Dataset Information

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

Publications

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

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