https://scholars.lib.ntu.edu.tw/handle/123456789/392546
Title: | Tumour exosome integrins determine organotropic metastasis. | Authors: | TANG-LONG SHEN | Issue Date: | Nov-2015 | Abstract: | Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis. ? 2015 Macmillan Publishers Limited. All rights reserved. |
URI: | http://europepmc.org/abstract/med/26524530 http://scholars.lib.ntu.edu.tw/handle/123456789/392546 |
DOI: | 10.1038/nature15756 | SDG/Keyword: | alpha6beta4 integrin; alphaVbeta5 integrin; protein kinase p60; protein S100B; very late activation antigen 6; alpha6beta4 integrin; alphaVbeta5 integrin; beta integrin; beta4 integrin; beta5 integrin; biological marker; integrin; protein S 100; very late activation antigen 6; vitronectin receptor; homeostasis; protein; tumor; animal cell; animal experiment; animal model; animal tissue; antibody specificity; Article; bone metastasis; cell therapy; controlled study; enzyme activation; enzyme phosphorylation; exosome; female; gene targeting; human; human cell; human tissue; liver metastasis; lung metastasis; major clinical study; mouse; nonhuman; oncogene src; priority journal; protein expression; proteomics; randomized controlled trial (topic); tumor cell; animal; antagonists and inhibitors; brain; C57BL mouse; cytology; endothelium cell; epithelium cell; exosome; fibroblast; genetics; Kupffer cell; liver; lung; metabolism; Neoplasm Metastasis; pathology; phosphorylation; tropism; tumor cell line; Animals; Biomarkers; Brain; Cell Line, Tumor; Endothelial Cells; Epithelial Cells; Exosomes; Female; Fibroblasts; Genes, src; Humans; Integrin alpha6beta1; Integrin alpha6beta4; Integrin beta Chains; Integrin beta4; Integrins; Kupffer Cells; Liver; Lung; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Organ Specificity; Phosphorylation; Receptors, Vitronectin; S100 Proteins; Tropism |
Appears in Collections: | 植物病理與微生物學系 |
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