MiR-200-containing extracellular vesicles promote breast cancer cell metastasis

Minh T.N. Le, Peter Hamar, Changying Guo, Emre Basar, Ricardo Perdigão-Henriques, Leonora Balaj, Judy Lieberman

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Abstract

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.

Original languageEnglish
Pages (from-to)5109-5128
Number of pages20
JournalJournal of Clinical Investigation
Volume124
Issue number12
DOIs
Publication statusPublished - Dec 1 2014

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Le, M. T. N., Hamar, P., Guo, C., Basar, E., Perdigão-Henriques, R., Balaj, L., & Lieberman, J. (2014). MiR-200-containing extracellular vesicles promote breast cancer cell metastasis. Journal of Clinical Investigation, 124(12), 5109-5128. https://doi.org/10.1172/JCI75695