Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier

• DOI: 10.1038/ncomms7716
• Publication Date: 2015-04-01T12:11:49Z
• Authors: Naoomi Tominaga; Nobuyoshi Kosaka; Makiko Ono; Takeshi Katsuda; Yusuke Yoshioka; Kenji Tamura; Jan Lötvall; Hitoshi Nakagama; Takahiro Ochiya
• Keywords: Extracellular Vesicles; Brain cancer; Extracellular vesicles

Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain the migration cells through blood-brain barrier (BBB). However, molecular mechanism behind passage this natural remains unclear. Here we show that cancer-derived extracellular vesicles (EVs), mediators cell-cell communication via delivery proteins and microRNAs (miRNAs), trigger breakdown BBB. Importantly, miR-181c promotes destruction BBB abnormal localization actin downregulation its target gene, PDPK1. PDPK1 degradation by leads to phosphorylated cofilin resultant activated cofilin-induced modulation dynamics. Furthermore, demonstrate systemic injection metastatic cell-derived EVs promoted cell lines are preferentially incorporated into vivo. Taken together, these results indicate a novel mediated triggers