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Series GSE68919 Query DataSets for GSE68919
Status Public on Jun 17, 2015
Title Tumor exosome integrins determine organotropic metastasis
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Stephen Paget first proposed, in 1889, that organ distribution of metastases is a non-random event, yet metastatic organotropism remains one of the greatest mysteries in cancer biology. Here, we demonstrate that exosomes released by lung-, liver- and brain-tropic tumor cells fuse preferentially with resident cells at their predicted destination, such as fibroblasts and epithelial cells in the lung, Kupffer cells in the liver, and endothelial cells in the brain. We found that exosome homing to organ-specific cell types prepares the pre-metastatic niche and that treatment with exosomes derived from lung tropic models can redirect metastasis to the lung. Proteomic profiling of exosomes revealed distinct integrin expression patterns associated with each organ-specific metastasis. Whereas exosomal integrins α6β4 and α6β1 were associated with lung metastasis, exosomal integrins αvβ5 and αvβ3 were linked with liver and brain metastases, respectively. Targeting α6β4 and αvβ5 integrins decreased exosome uptake and metastasis in the lung and liver, respectively. Importantly, we demonstrate that exosome uptake activates a cell-specific subset of S100 family genes, known to support cell migration and niche formation. Finally, our clinical data indicate that integrin-expression profiles in circulating plasma exosomes from cancer patients could be used to predict organ-specific metastasis.
Overall design Education of human von Kupffer cells in vitro with human pancreatic cancer exosomes
Contributor(s) Hoshino A, Costa-Silva B, Shen T, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kosaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Ararso Y, Zhang T, Kure EH, Mallya K, Batra SK, Vinagolu RK, Fodstad O, Muller V, Pantel K, Bissell MJ, Ghajar C, Garcia BA, Kang Y, Matei I, Peinado H, Bromberg J, Lyden D
Citation(s) 25985394, 26524530
Submission date May 15, 2015
Last update date Jul 26, 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 (8)
GSM1686446 BxPc3 Beta5 integrin KD exo 1
GSM1686447 BxPc3 Beta5 integrin KD exo 2
GSM1686448 Control 1
BioProject PRJNA284109
SRA SRP058375

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE68919_Processed_BxPc3exo_vs_Beta5KD.txt.gz 1.4 Mb (ftp)(http) TXT
GSE68919_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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