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

Torii, Chisaho; Maishi, Nako; Kawamoto, Taisuke; Morimoto, Masahiro; Akiyama, Kosuke; Yoshioka, Yusuke; Minami, Takashi; Tsumita, Takuya; Alam, Mohammad Towfik; Ochiya, Takahiro; Hida, Yasuhiro; Hida, Kyoko

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

Torii, Chisaho; Maishi, Nako; Kawamoto, Taisuke et al.

Scientific reports, 2021, 11(1), 13502

Permalink : https://hdl.handle.net/2115/82593

このアイテムのアクセス数:569件（2026-08-10 20:13 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/82593
タイトル	miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells
著者	Torii, Chisaho ; Maishi, Nako ; Kawamoto, Taisuke ; Morimoto, Masahiro ; Akiyama, Kosuke ; Yoshioka, Yusuke ; Minami, Takashi ; Tsumita, Takuya ; Alam, Mohammad Towfik ; Ochiya, Takahiro ; Hida, Yasuhiro ; Hida, Kyoko
e-Rad_Researcher 00780561 著者名 Torii, Chisaho
e-Rad_Researcher 00632423 著者名 Maishi, Nako
著者名 Kawamoto, Taisuke
著者名 Morimoto, Masahiro
e-Rad_Researcher 10609100 著者名 Akiyama, Kosuke
著者名 Yoshioka, Yusuke
著者名 Minami, Takashi
著者名 Tsumita, Takuya
e-Rad_Researcher 60641694 著者名 Alam, Mohammad Towfik
e-Rad_Researcher 60192530 著者名 Ochiya, Takahiro
e-Rad_Researcher 30399919 著者名 Hida, Yasuhiro
e-Rad_Researcher 40399952 著者名 Hida, Kyoko
言語	英語
発行日	2021-07-05
出版者	Nature Research
収録物名	Scientific reports
巻(号)	11(1)
ページ	13502
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	2045-2322
関連情報	PMID 34226586
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1038/s41598-021-92879-5