Metastasis is associated with poor prognosis in breast cancer patients. Not all cancer
cells within a tumor are capable of metastasizing. The microRNA-200 (miR-200) family,
which regulates the mesenchymal-to-epithelial transition, is enriched in the serum
of patients with metastatic cancers. Ectopic expression of miR-200 can confer metastatic
ability to poorly metastatic tumor cells in some settings. Here, we investigated whether
metastatic capability could be transferred between metastatic and nonmetastatic cancer
cells via extracellular vesicles. miR-200 was secreted in extracellular vesicles from
metastatic murine and human breast cancer cell lines, and miR-200 levels were increased
in sera of mice bearing metastatic tumors. In culture, murine and human metastatic
breast cancer cell extracellular vesicles transferred miR-200 microRNAs to nonmetastatic
cells, altering gene expression and promoting mesenchymal-to-epithelial transition.
In murine cancer and human xenograft models, miR-200 expressing tumors and extracellular
vesicles from these tumors promoted metastasis of otherwise weakly metastatic cells
either nearby or at distant sites and conferred to these cells the ability to colonize
distant tissues in a miR-200 dependent manner. Together, our results demonstrate that
metastatic capability can be transferred by the uptake of extracellular vesicles.
