@article{87976,
  keywords = {Animals, Humans, phosphorylation, Biomarkers, Mice, Mice, Inbred C57BL, Female, Cell Line, Tumor, Organ Specificity, Fibroblasts, Brain, Epithelial Cells, Integrins, Receptors, Vitronectin, Integrin beta Chains, Liver, Endothelial Cells, Tropism, Neoplasm Metastasis, Exosomes, Genes, src, Integrin alpha6beta1, Integrin alpha6beta4, Integrin beta4, Kupffer Cells, Lung, S100 Proteins},
  author = {Ayuko Hoshino and Bruno Costa-Silva and Tang-Long Shen and Goncalo Rodrigues and Ayako Hashimoto and Milica Tesic Mark and Henrik Molina and Shinji Kohsaka and Angela Di Giannatale and Sophia Ceder and Swarnima Singh and Caitlin Williams and Nadine Soplop and Kunihiro Uryu and Lindsay Pharmer and Tari King and Linda Bojmar and Alexander Davies and Yonathan Ararso and Tuo Zhang and Haiying Zhang and Jonathan Hernandez and Joshua Weiss and Vanessa Dumont-Cole and Kimberly Kramer and Leonard Wexler and Aru Narendran and Gary Schwartz and John Healey and Per Sandstrom and Knut J{\o}rgen Labori and Elin Kure and Paul Grandgenett and Michael Hollingsworth and de Maria Sousa and Sukhwinder Kaur and Maneesh Jain and Kavita Mallya and Surinder Batra and William Jarnagin and Mary Brady and Oystein Fodstad and Volkmar Muller and Klaus Pantel and Andy Minn and Mina Bissell and Benjamin Garcia and Yibin Kang and Vinagolu Rajasekhar and Cyrus Ghajar and Irina Matei and Hector Peinado and Jacqueline Bromberg and David Lyden},
  title = {Tumour exosome integrins determine organotropic metastasis.},
  abstract = {<p>Ever since Stephen Paget{\textquoteright}s 1889 hypothesis, metastatic organotropism has remained one of cancer{\textquoteright}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.</p>
},
  year = {2015},
  journal = {Nature},
  volume = {527},
  pages = {329-35},
  month = {11/2015},
  issn = {1476-4687},
  doi = {10.1038/nature15756},
  language = {eng},
}