Tumour exosome integrins determine organotropic metastasis [electronic resource]

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Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 571.6 Cell biology

Thông tin xuất bản: Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2015

Mô tả vật lý: Size: p. 329-335 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 261024

 Ever since Stephen Paget?s 1889 hypothesis, metastatic organotropism has remained one of cancer?s greatest mysteries. In this paper, 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 ?<
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  were associated with lung metastasis, while exosomal integrin ?<
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  was linked to liver metastasis. Targeting the integrins ?<
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  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. In conclusion, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
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