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Colorectal cancer cell-derived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML down-regulation in endothelial cells
Institution:1. United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 yanagido, Gifu-city, Gifu 501-1193, Japan;2. Department of Gastroenterology, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake-shi, Aichi 470-1192, Japan;3. Department of Hematology and Oncology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan;1. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China;2. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China
Abstract:Emerging studies on circulating microRNAs (miRNAs) or microvesicles (MVs) have shown the potential of them to be novel biomarkers and therapeutic targets for cancer. However, the biological roles of these miRNAs and MVs have not been validated yet. To determine the biological significance of MVs, we used human colorectal cancer cells as the MV donor and endothelial cells (HUVECs) as the MV recipient and demonstrated the transfer of colorectal cancer cell-derived MVs (CRC-MVs) to HUVECs and evaluated the roles of these MVs and their cargo in tumor angiogenesis. Consequently, the incubation of HUVECs with CRC-MVs promoted the proliferation, migration, and tube formation activities of these cells. Among the cargoes shuttled by the MVs, miR-1246 and TGF-β were considered to be responsible for the pro-angiogenic function of MVs by activating Smad 1/5/8 signaling in the HUVECs. These results suggest that colorectal cancer cells secreted MVs to contribute to tumor angiogenesis.
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