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Tumour exosome integrins determine organotropic metastasis
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- Hoshino, Ayuko (författare)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Costa-Silva, Bruno (författare)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Shen, Tang-Long (författare)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; National Taiwan University, Taiwan; National Taiwan University, Taiwan
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- 2015-10-28
- 2015
- Engelska.
- Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 527:7578, s. 329-
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Ever since Stephen Pagets 1889 hypothesis, metastatic organotropism has remained one of cancers 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 alpha(6)beta(4) and alpha(6)beta(1) were associated with lung metastasis, while exosomal integrin alpha(v)beta(5) was linked to liver metastasis. Targeting the integrins alpha(6)beta(4) and alpha(v)beta(5) 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
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