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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
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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.
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Overall design |
Normal pancreas and Pancreatic cancer exosomes education of human von Kupffer cells in vitro
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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 |
E-mail(s) |
dcl2001@med.cornell.edu
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Organization name |
Weill Medical College of Cornell University
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Department |
Departments of Pediatrics, Cell & Developmental Biology
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Street address |
413 E. 69th St., 12th Floor, BB-1251
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City |
New York |
State/province |
NY |
ZIP/Postal code |
10021 |
Country |
USA |
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Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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Samples (4)
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Relations |
BioProject |
PRJNA278149 |
SRA |
SRP056146 |
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 |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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