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Series GSE137236 Query DataSets for GSE137236
Status Public on Aug 12, 2020
Title Endocrine-exocrine signaling in obesity-driven pancreatic ductal adenocarcinoma
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Obesity is a major modifiable risk factor for pancreatic ductal adenocarcinoma (PDAC), yet how and when obesity contributes to PDAC progression is not well understood. Leveraging an autochthonous mouse model, we demonstrate a causal and reversible role for obesity in early PDAC progression, showing that obesity markedly enhances tumorigenesis, while genetic or dietary induction of weight loss intercepts cancer development. Bulk and single cell molecular analyses of human and murine samples define microenvironmental consequences of obesity that promote tumor development rather than new driver gene mutations. We observe increased inflammation and fibrosis and also provide evidence for significant pancreatic islet cell adaptation in obesity-associated tumors. Specifically, we identify aberrant beta islet cell expression of the peptide hormone cholecystokinin (CCK) in tumors as an adaptive response to obesity. Furthermore, islet CCK expression promotes oncogenic Kras-driven pancreatic ductal tumorigenesis. Our studies argue that PDAC progression is driven by local obesity-associated changes in the tumor microenvironment – rather than systemic effects – and implicate endocrine-exocrine signaling beyond insulin in PDAC development. Furthermore, our demonstration that these obesity-associated adaptations are reversible supports the use of anti-obesity strategies to intercept PDAC early during progression.
Overall design Islets from pancreata from ob/ob and wild-type (WT) mice
Contributor(s) Chung KM, Singh J, Lawres L, Dorans KJ, Garcia C, Burkhardt DB, Robbins R, Bhutkar A, Cardone R, Zhao X, Babic A, Vayrynen SA, Costa AD, Nowak JA, Chang DT, Dunne RF, Hezel AF, Koong AC, Wilhelm JJ, Bellin MD, Nylander V, Gloyn AL, McCarthy MI, Kibbey RG, Krishnaswamy S, Wolpin BM, Jacks T, Fuchs CS, Muzumdar MD
Citation(s) 32304665
Submission date Sep 10, 2019
Last update date Aug 12, 2020
Contact name Daniel Burkhardt
Organization name Cellarity
Street address 101 South Street, 6th Floor
City Somerville
State/province MA
ZIP/Postal code 02145
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM4073727 wt
GSM4073728 ob/ob
BioProject PRJNA564842
SRA SRP221287

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Supplementary file Size Download File type/resource
GSE137236_filtered_counts.normalized.csv.gz 51.5 Mb (ftp)(http) CSV
GSE137236_metadata.csv.gz 430.8 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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