Pre-neoplastic pancreas cells enter a partially mesenchymal state following transient TGF-β exposure.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease and a major health problem in the United States. While the cytokine TGF-β has been implicated in PDAC development, it can exert both pro-tumorigenic and anti-tumorigenic effects that are highly context dependent and incompletely understood. Using three-dimensional (3D) cultures of Kras^G12D-expressing mouse pancreatic epithelial cells we demonstrated that while exposure to exogenous TGF-β induced growth arrest of the Kras^G12D cells, its subsequent removal allowed the cells to enter a hyper-proliferative, partially mesenchymal (PM), and progenitor-like state. This state was highly stable and was maintained by autocrine TGF-β signaling. While untreated Kras^G12D cells formed cystic lesions in vivo, PM

SUBMITTER: Handler J 

PROVIDER: S-EPMC6076343 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature