GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE43770 Query DataSets for GSE43770
Status Public on Oct 03, 2014
Title Vitamin d receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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 activation reduces expression in PSCs of genes implicated in activation, inflammation, and extracellular matrix production, as well as restoring lipid droplet integrity. In vivo, the VDR ligand calcipotriol enhances the anti-tumor effects of gemcitabine by increasing intratumoral concentration 5-fold, reducing tumor volume to near baseline and lowering metastases by more than 65%. These findings implicate VDR as a master regulator of PSC activation and identify a novel therapeutic approach for the treatment of pancreatic cancer.
Overall design RNA-Seq analyses was used to characterize cancer-associated changes between pre-activated (3-day culture) and activated (7-day culture) primary mouse PSCs, as well as control and PDA human PSCs. RNA-Seq was also used to assess the impact of VDR activation (DMSO vs calcipotriol) in a human PSC line (MiaPaCa-2), the mouse primary PSCs
Contributor(s) Yu RT, Sherman MH, Evans RM
Citation(s) 25259922
Submission date Jan 25, 2013
Last update date May 15, 2019
Contact name Ruth T Yu
Organization name Salk Institute
Department Gene Expression Lab
Lab Ronald Evans
Street address 10010 N Torrey Pines Rd
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (17)
GSM1070765 PSC from PDA patient [CA2]
GSM1070766 PSC from PDA patient [CA3]
GSM1070767 PSC from PDA patient [CA6]
SRA SRP018218
BioProject PRJNA187388

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource 60.7 Mb (ftp)(http) BW 61.6 Mb (ftp)(http) BW
GSE43770_RAW.tar 1.1 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap