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Hoshino et al. Metastasis to specific organs is determined by tumor exosome integrins



DOI:10.1038/bonekey.2016.27

The mechanisms underlying organ-specific metastasis have remained a mystery for over 125 years, since Stephen Paget first proposed its existence. In this new and ground-breaking study, several important findings by Hoshino et al. go a long way to solving the puzzle.

Firstly, they demonstrate that the biodistribution of tumour-derived exosomes in vivo matches the organotropic distribution of the metastatic cancer cells from which they are derived. They also show that exosomal integrins determine the organotropism of exosomes; for example, exosomal integrins α6β4 and α6β1 are most abundant in lung-tropic exosomes, while αvβ5 is associated predominantly with metastasis to the liver.

It further becomes clear from the study that exosomal integrins activate pro-inflammatory S100 genes in specific resident fibroblast and Kupffer cells within lungs and liver, respectively, thereby preparing the pre-metastatic niche. Finally, the researchers show that exosomal integrin beta4 and alpha v can be used as serum biomarkers in the clinic for predicting spread of breast and pancreatic cancer to the lungs and liver, respectively.

Editor’s comment: Overall, this study demonstrates an important role for tumor-derived exosomes in dictating organ-specific metastasis. The findings may lead on to further research into diagnostic methods and, possibly, therapeutic interventions to discourage spread of these cancers to distant sites.


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