Visualization of exosome-mediated miR-210 transfer from hypoxic tumor cells

// Kyung Oh Jung 1, 2, 3, 5 , Hyewon Youn 1, 3, 4 , Chul-Hee Lee 1, 2, 3 , Keon Wook Kang 1, 3 , June-Key Chung 1, 2, 3 1 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea, 110-799 2 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea, 110-799 3 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea, 110-799 4 Cancer Imaging Center, Seoul National University Hospital, Seoul, Korea, 110-799 5 Current affiliation: Department of Radiation Oncology & Medical Physics, Stanford University, CA, USA, 94305 Correspondence to: Hyewon Youn, email: hwyoun@snu.ac.kr June-key Chung, email: jkchung@snu.ac.kr Keywords: exosome, breast cancer, miR-210, tumor microenvironment, hypoxia Received: August 01, 2016      Accepted: December 01, 2016      Published: December 27, 2016 ABSTRACT Cancer cells actively release exosomes carrying specific cellular components, such as proteins, mRNA, and miRNA, to communicate with various cells in the tumor microenvironment. We visualized exosome-mediated transfer of miR-210 from hypoxic breast cancer cells to neighboring cells using a miR-210 specific reporter system. By in vitro and in vivo visualization, we found that exosomes with miR-210 were transferred to cells in the tumor microenvironment and that miR-210 was involved in expression of vascular remodeling related genes, such as Ephrin A3 and PTP1B, to promote angiogenesis. These results indicate that cellular components, such as miRNAs from hypoxic cancer cells, spread to adjacent cancer cells in the tumor microenvironment via exosomes and influence tumor progression.