Tumour exosome integrins determine organotropic metastasis.
Nature
; 527(7578): 329-35, 2015 Nov 19.
Article
em En
| MEDLINE
| ID: mdl-26524530
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 α6ß4 and α6ß1 were associated with lung metastasis, while exosomal integrin αvß5 was linked to liver metastasis. Targeting the integrins α6ß4 and αvß5 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Integrinas
/
Tropismo
/
Exossomos
/
Fígado
/
Pulmão
/
Metástase Neoplásica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
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Humans
Idioma:
En
Revista:
Nature
Ano de publicação:
2015
Tipo de documento:
Article