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miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells

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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
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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