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Hokkaido University Collection of Scholarly and Academic Papers >
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miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells
| Title: | miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells |
| Authors: | Torii, Chisaho Browse this author →KAKEN DB | | Maishi, Nako Browse this author →KAKEN DB | | Kawamoto, Taisuke Browse this author | | Morimoto, Masahiro Browse this author | | Akiyama, Kosuke Browse this author →KAKEN DB | | Yoshioka, Yusuke Browse this author | | Minami, Takashi Browse this author | | Tsumita, Takuya Browse this author | | Alam, Mohammad Towfik Browse this author →KAKEN DB | | Ochiya, Takahiro Browse this author →KAKEN DB | | Hida, Yasuhiro Browse this author →KAKEN DB | | Hida, Kyoko Browse this author →KAKEN DB |
| Issue Date: | 5-Jul-2021 |
| Publisher: | Nature Research |
| Journal Title: | Scientific reports |
| Volume: | 11 |
| Issue: | 1 |
| Start Page: | 13502 |
| Publisher DOI: | 10.1038/s41598-021-92879-5 |
| PMID: | 34226586 |
| Abstract: | Tumor endothelial cells (TECs) reportedly exhibit altered phenotypes. We have demonstrated that TECs acquire drug resistance with the upregulation of P-glycoprotein (P-gp, ABCB1), contrary to traditional assumptions. Furthermore, P-gp expression was higher in TECs of highly metastatic tumors than in those of low metastatic tumors. However, the detailed mechanism of differential P-gp expression in TECs remains unclear. miRNA was identified in highly metastatic tumor extracellular vesicles (EVs) and the roles of miRNA in endothelial cell resistance were analyzed in vitro and in vivo. In the present study, we found that treatment of highly metastatic tumor-conditioned medium induced resistance to 5-fluorouracil (5-FU) with interleukin-6 (IL-6) upregulation in endothelial cells (ECs). Among the soluble factors secreted from highly metastatic tumors, we focused on EVs and determined that miR-1246 was contained at a higher level in highly metastatic tumor EVs than in low metastatic tumor EVs. Furthermore, miR-1246 was transported via the EVs into ECs and induced IL-6 expression. Upregulated IL-6 induced resistance to 5-FU with STAT3 and Akt activation in ECs in an autocrine manner. These results suggested that highly metastatic tumors induce drug resistance in ECs by transporting miR-1246 through EVs. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82593 |
| Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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