Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17970
Título
Tumour exosome integrins determine organotropic metastasis.
Autor(es)
Hoshino, Ayuko | Costa-Silva, Bruno | Shen, Tang-Long | Rodrigues, Goncalo | Hashimoto, Ayako | Tesic Mark, Milica | Molina, Henrik | Kohsaka, Shinji | Di Giannatale, Angela | Ceder, Sophia | Singh, Swarnima | Williams, Caitlin | Soplop, Nadine | Uryu, Kunihiro | Pharmer, Lindsay | King, Tari | Bojmar, Linda | Davies, Alexander E | Ararso, Yonathan | Zhang, Tuo | Zhang, Haiying | Hernandez, Jonathan | Weiss, Joshua M | Dumont-Cole, Vanessa D | Kramer, Kimberly | Wexler, Leonard H | Narendran, Aru | Schwartz, Gary K | Healey, John H | Sandstrom, Per | Labori, Knut Jørgen | Kure, Elin H | Grandgenett, Paul M | Hollingsworth, Michael A | de Sousa, Maria | Kaur, Sukhwinder | Jain, Maneesh | Mallya, Kavita | Batra, Surinder K | Jarnagin, William R | Brady, Mary S | Fodstad, Oystein | Muller, Volkmar | Pantel, Klaus | Minn, Andy J | Bissell, Mina J | Garcia, Benjamin A | Kang, Yibin | Rajasekhar, Vinagolu K | Ghajar, Cyrus M | Matei, Irina | Peinado, Hector | Bromberg, Jacqueline | Lyden, David
Fecha de publicación
2015-11-19
Cita
Nature . 2015 ;527(7578):329-35
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Tropism | 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
Versión en línea
DOI
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