At sites of metastasis, tumor cells influence resident stromal cells to enable metastatic colonization and growth. Weiying Zhou and colleagues now show that tumor cells use a microRNA, delivered by exosomes to the endothelium, to increase vascular permeability and metastasis (Cancer Cell 25, 501–515, 2014).
The researchers identified miR-105 in a screen for microRNAs in exosomes released by a human metastatic breast tumor cell line that could stimulate endothelial cell migration. By targeting the tight junction protein ZO-1, miR-105 delivered in exosomes to endothelial cell monolayers increased both the permeability of the monolayers and the ability of tumor cells to invade across them. In mice, delivery of miR-105–containing exosomes or overexpression of miR-105 in metastatic breast cancer tumor cell xenografts decreased endothelial ZO-1 expression and increased vascular permeability and metastasis, whereas miR-105 knockdown had the opposite effects.
In early-stage breast cancer patients, the authors detected miR-105 in exosomes in the blood and found that the levels of circulating or tumor miR-105 were inversely correlated with the level of tumor ZO-1 expression. The levels of circulating or tumor miR-105 were higher in patients who later developed distant metastases, suggesting the possible use of miR-105 as a predictive biomarker.
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Basson, M. Tumor cells unlock the endothelium. Nat Med 20, 482 (2014). https://doi.org/10.1038/nm.3576
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DOI: https://doi.org/10.1038/nm.3576