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Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia

ABSTRACT: Many human cancers are dramatically accelerated in the setting of chronic inflammation. However the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that KrasG12D induces expression of functional IL-17 receptors on PanIN cells, and stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by chronic pancreatitis, resulting in functional in vivo changes in gene expression among PanIN epithelial cells. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation.

ORGANISM(S): Mus musculus

PROVIDER: GSE54753 | GEO | 2016/02/03

SECONDARY ACCESSION(S): PRJNA237551

REPOSITORIES: GEO

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