Vitamin d receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy

ABSTRACT: The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) has been attributed to intrinsic resistance to chemotherapy and a growth-permissive tumor microenvironment. Quiescent pancreatic stellate cells (PSCs) are neuroendocrine, nestin-positive, lipid-accumulating cells whose homologues in the liver are the principal repository of Vitamin A esters. Upon activation, lipid droplets are lost and via transdifferentiation they become the key cell type responsible for driving the severe desmoplasia that characterizes PDA. Despite their critical role in PDA progression and chemoresistance, therapeutic strategies targeting PSCs are lacking. Here we identified the vitamin D receptor (VDR) as a master genomic regulator of PSC activation and function. In vitro we demonstrate that VDR a

ORGANISM(S): Homo sapiens

SUBMITTER: Sherman MH 

PROVIDER: S-ECPF-GEOD-43770 | biostudies-other | 2014 Sep

REPOSITORIES: biostudies-other