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Series GSE66876 Query DataSets for GSE66876
Status Public on Mar 16, 2015
Title Pancreatic cancer exosomes induce pre-metastatic niche formation in the liver
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Pancreatic cancers (PCs) are highly metastatic with poor prognosis, mainly due to delayed detection. We hypothesized that intercellular communication is critical for metastatic progression. Here, we show that PC-derived exosomes induce liver pre-metastatic niche formation in naïve mice and consequently increase liver metastatic burden. Uptake of PC-derived exosomes by Kupffer cells caused transforming growth factor β secretion and upregulation of fibronectin production by hepatic stellate cells. This fibrotic microenvironment enhanced recruitment of bone marrow-derived macrophages. We found that macrophage migration inhibitory factor (MIF) was highly expressed in PC-derived exosomes, and its blockade prevented liver pre-metastatic niche formation and metastasis. Compared to patients whose pancreatic tumors did not progress, MIF was markedly higher in exosomes from stage I PC patients who later developed liver metastasis. These findings suggest that exosomal MIF primes the liver for metastasis and may be a prognostic marker for the development of PC liver metastasis.
Overall design Normal pancreas and Pancreatic cancer exosomes education of human von Kupffer cells in vitro
Contributor(s) Costa-Silva B, Aiello NM, Singh S, Zhang H, Thakur BK, Becker A, Hoshino A, Mark MT, Molina H, Xiang J, Zhang T, Theilen T, García-Santos G, Williams C, Ararso Y, Huang Y, Rodrigues G, Shen T, Labori K, Bowitz Lothe IM, Kure EH, Ocean AJ, Hernandez J, Doussat A, Ebbesen S, Jain M, Mallya K, Batra SK, Jarnagin WR, Schwartz RE, Matei I, Peinado H, Stanger BZ, Bromberg J, Lyden D
Citation(s) 25985394
Submission date Mar 13, 2015
Last update date May 15, 2019
Contact name David Lyden
Organization name Weill Medical College of Cornell University
Department Departments of Pediatrics, Cell & Developmental Biology
Street address 413 E. 69th St., 12th Floor, BB-1251
City New York
State/province NY
ZIP/Postal code 10021
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (4)
GSM1633689 PAN02EXO
GSM1633690 Human_Kupffer_Cells_Control
BioProject PRJNA278149
SRA SRP056146

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE66876_Processed_CTLexo_vs_PAN02exo.txt.gz 1.5 Mb (ftp)(http) TXT
GSE66876_Processed_Control_vs_BxPc3exo.txt.gz 1.5 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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