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

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 tumor...

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Autores principales:	Chisaho Torii, Nako Maishi, Taisuke Kawamoto, Masahiro Morimoto, Kosuke Akiyama, Yusuke Yoshioka, Takashi Minami, Takuya Tsumita, Mohammad Towfik Alam, Takahiro Ochiya, Yasuhiro Hida, Kyoko Hida
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a962533b48404974bf9badee9b69b8ef
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spelling	oai:doaj.org-article:a962533b48404974bf9badee9b69b8ef2021-12-02T18:34:06ZmiRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells10.1038/s41598-021-92879-52045-2322https://doaj.org/article/a962533b48404974bf9badee9b69b8ef2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92879-5https://doaj.org/toc/2045-2322Abstract 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.Chisaho ToriiNako MaishiTaisuke KawamotoMasahiro MorimotoKosuke AkiyamaYusuke YoshiokaTakashi MinamiTakuya TsumitaMohammad Towfik AlamTakahiro OchiyaYasuhiro HidaKyoko HidaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chisaho Torii Nako Maishi Taisuke Kawamoto Masahiro Morimoto Kosuke Akiyama Yusuke Yoshioka Takashi Minami Takuya Tsumita Mohammad Towfik Alam Takahiro Ochiya Yasuhiro Hida Kyoko Hida miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells
description	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.
format	article
author	Chisaho Torii Nako Maishi Taisuke Kawamoto Masahiro Morimoto Kosuke Akiyama Yusuke Yoshioka Takashi Minami Takuya Tsumita Mohammad Towfik Alam Takahiro Ochiya Yasuhiro Hida Kyoko Hida
author_facet	Chisaho Torii Nako Maishi Taisuke Kawamoto Masahiro Morimoto Kosuke Akiyama Yusuke Yoshioka Takashi Minami Takuya Tsumita Mohammad Towfik Alam Takahiro Ochiya Yasuhiro Hida Kyoko Hida
author_sort	Chisaho Torii
title	miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells
title_short	miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells
title_full	miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells
title_fullStr	miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells
title_full_unstemmed	miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells
title_sort	mirna-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a962533b48404974bf9badee9b69b8ef
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miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells

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