Dataset Information

Expression data from 1499 cells, a mouse ADM/PanIN1-derived pancreatic ductal cell line, and the mouse pancreatic ductal adenocarcinoma (PDAC) AH375 cell line.

ABSTRACT: In a Kras-driven mouse model of multistage pancreatic cancer progression, decreased p-ERK levels correlate with tumor initiation. In cells derived from this model, transformed cells with low p-ERK levels express markers of pluripotency and demonstrate phenotypes of tumor initiating cells, such as formation of free-floating tumor spheres. Here, a comparison of gene expression from the 1499 cell line, which are premalignant cells isolated from mouse ADM (acinar-to-ductal metaplasia) and PanIN1 (pancreatic intraepithelial lesions), and the AH375 cell line, established from mouse PDAC, was performed.

ORGANISM(S): Mus musculus

PROVIDER: GSE57566 | GEO | 2016/05/10

SECONDARY ACCESSION(S): PRJNA246713

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by desmoplastic stroma surrounding most tumors. Activated stromal fibroblasts, namely Cancer-associated fibroblasts (CAFs), play a major role in PDAC progression. Here we analyzed if CAFs influence acinar cells and impact PDAC initiation, namely “Acinar to Ductal Metaplasia” (ADM). ADM connection with PDAC pathophysiology is indicated but not yet established. Hence, we hypothesized that CAF secretome might play a significant role in ADM in PDAC initiation. Mouse and human acinar cell organoids, acinar cells cocultured with CAFs and exposed to CAF-conditioned media (CAF-CM), acinar cell explants, and CAF cocultures, etc., were examined by qRT-PCR, RNA-seq, immunoblotting and confocal microscopy. Data from LC-MS/MS analysis of CAF CM and RNAseq data of acinar cells post-CM exposure were integrated using bioinformatics tools to identify molecular mechanism for CAF-induced ADM. Using confocal microscopy, immunoblotting, and qRT-PCR analysis, we validated the depletion of key signaling axis in cell-line, acinar explant coculture, and mCAFs. Close association of acino-ductal (UEA1, Amylase, Ck19) markers and mCAFs (α-SMA) in LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1Cre (KPC) and LSL-KrasG12D/+; Pdx1Cre (KC) autochthonous progression tumor tissue was observed. Caerulein treatment-induced mCAFs increased Ck19 and decreased Amylase in wild-type (WT) and KC pancreas. Likewise, acinar-mCAF cocultures revealed induction of ductal transdifferentiation in cell-line, acinar-organoid, and explant coculture formats in WT and KC mice pancreas. Proteomic and transcriptomic data integration revealed a novel Laminin5/Integrinα4/Stat3 axis responsible for CAF-mediated acinar to ductal cell transdifferentiation. Results collectively suggest the first evidence for CAF-influenced acino-ductal phenotypic switchover, thus highlighting the role of the tumor micro-environment in the inception of pancreatic carcinogenesis.

Dataset Information

Expression data from 1499 cells, a mouse ADM/PanIN1-derived pancreatic ductal cell line, and the mouse pancreatic ductal adenocarcinoma (PDAC) AH375 cell line.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets