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Cancer genetics

Exosomally derived miR-105 destroys tight junctions

Nature Reviews Genetics volume 15, page 362 (2014)Cite this article

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Exosomes are small secretory vesicles that are released into the extracellular environment and can also be taken up by recipient cells. To study the effect of cancer-secreted exosomes on the endothelium, Zhou et al. used human microvascular endothelial cells (HMVECs) and incubated them with purified fluorescently labelled exosomes that were derived from either MDA-MB-231 metastatic breast cancer cells or the non-cancerous mammary epithelial cell line MCF-10A. Although HMVECs took up both cancer-derived and non-cancer-derived exosomes with high efficiency (>90%), HMVECs incubated with the cancer-derived exosomes showed significantly higher migration efficiency in a transwell migration assay. This effect was recapitulated when HMVECs were incubated with small RNAs or total RNA from cancer-derived exosomes but not from non-cancer-derived exosomes.

In order to determine the specific small RNA that induced migration in cancer-derived exosomes, small RNAs from exosomes derived from MDA-MB-231 and MCF-10A cells were sequenced and profiled. The secretion of the miRNA miR-105 was found to be specific to MDA-MB-231 cells, and its expression level was significantly higher in exosomes derived from MDA-MB-231 cells than in exosomes derived from MCF-10A cells. Moreover, when the authors examined a panel of breast cancer lines, the expression and secretion of miR-105 were specific to highly metastatic lines.

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References

  1. Zhou, W. et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell 25, 501–515 (2014)

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  1. Isabel Lokody
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Lokody, I. Exosomally derived miR-105 destroys tight junctions. Nat Rev Genet 15, 362 (2014). https://doi.org/10.1038/nrg3741

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