Extracellular vesicle-mediated Transfer of miRNA-1 from Primary tumor Repress Distant Metastasis Growth

Abstract Metastases originate from primary tumors and conquer distant organs. Growing evidence suggest that metastases are under control of primary tumors even out of the primary territory, however, how primary tumors remotely control metastases remains unclear. Here, we discovered a molecular mechanism by which a primary tumor suppresses the metastatic growth. Interestingly, we found that extracellular vesicles (EVs) derived from a primary tumor has an ability to inhibit the growth of metastases in vitro and in vivo. miR-1 was particularly enriched in the primary tumor-derived EVs (pTDEs) and responsible for the suppression of metastatic growth. Mechanistically, intracellular ROS and DNA damage were induced, which led to the cell cycle arrest. Collectively, our data demonstrate that the primary tumor restricts distant metastatic cancer by miR-1 in pTDEs which can potentially be used as an anticancer drug for metastasis.