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

Abstract

AbstractMetastases originate from primary tumors that conquer distant organs. Growing evidence suggests that metastases are still under primary tumor dominance, even out of the primary territory. However, the mechanism by which primary tumors prime the fate of metastasis is unclear. Here, we investigated the influence of primary tumor-derived extracellular vesicles (pTDEs) on distant metastasis. Metastatic growth was remarkably suppressed when cells were treated with pTDEsin vitroand intravenously in a spontaneous metastatic mouse model. pTDEs from primary tumors with cancer stem cell (CSC) characteristics inhibit metastatic growth by inducing intracellular ROS/DNA double-stranded damage, thus inhibiting G2/M phase accumulation. We found that miR-1 was the most abundant in pTDEs and showed a stronger inhibitory effect when miR-1 was overloaded in pTDEs. Collectively, we demonstrated that the primary tumor could control distant metastatic cancer via primary tumor-derived EV-miR-1. Additionally, our approach suggests the development of anticancer drugs for metastasis based on pTDE-miR-1.