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Intraperitoneal transfer of microRNA‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer

Small extracellular vesicles (sEV) contain various microRNAs (miRNAs) and play crucial roles in the tumor metastatic process. Although miR‐29b levels in peritoneal exosomes were markedly reduced in patients with peritoneal metastases (PM), their role has not been fully clarified. In this study, we a...

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Autores principales: Kimura, Yuki, Ohzawa, Hideyuki, Miyato, Hideyo, Kaneko, Yuki, Kuchimaru, Takahiro, Takahashi, Rei, Yamaguchi, Hironori, Kurashina, Kentaro, Saito, Shin, Hosoya, Yoshinori, Lefor, Alan Kawarai, Sata, Naohiro, Kitayama, Joji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323101/
https://www.ncbi.nlm.nih.gov/pubmed/36939028
http://dx.doi.org/10.1111/cas.15793
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author Kimura, Yuki
Ohzawa, Hideyuki
Miyato, Hideyo
Kaneko, Yuki
Kuchimaru, Takahiro
Takahashi, Rei
Yamaguchi, Hironori
Kurashina, Kentaro
Saito, Shin
Hosoya, Yoshinori
Lefor, Alan Kawarai
Sata, Naohiro
Kitayama, Joji
author_facet Kimura, Yuki
Ohzawa, Hideyuki
Miyato, Hideyo
Kaneko, Yuki
Kuchimaru, Takahiro
Takahashi, Rei
Yamaguchi, Hironori
Kurashina, Kentaro
Saito, Shin
Hosoya, Yoshinori
Lefor, Alan Kawarai
Sata, Naohiro
Kitayama, Joji
author_sort Kimura, Yuki
collection PubMed
description Small extracellular vesicles (sEV) contain various microRNAs (miRNAs) and play crucial roles in the tumor metastatic process. Although miR‐29b levels in peritoneal exosomes were markedly reduced in patients with peritoneal metastases (PM), their role has not been fully clarified. In this study, we asked whether the replacement of miR‐29b can affect the development of PM in a murine model. UE6E7T‐12, human bone marrow‐derived mesenchymal stem cells (BMSCs), were transfected with miR‐29b‐integrating recombinant lentiviral vector and sEV were isolated from culture supernatants using ultracentrifugation. The sEV contained markedly increased amounts of miR‐29b compared with negative controls. Treatment with transforming growth factor‐β1 decreased the expression of E‐cadherin and calretinin with increased expression of vimentin and fibronectin on human omental tissue‐derived mesothelial cells (HPMCs). However, the effects were totally abrogated by adding miR‐29b‐rich sEV. The sEV inhibited proliferation and migration of HPMCs by 15% (p < 0.005, n = 6) and 70% (p < 0.005, n = 6), respectively, and inhibited adhesion of NUGC‐4 and MKN45 to HPMCs by 90% (p < 0.0001, n = 5) and 77% (p < 0.0001, n = 5), respectively. MicroRNA‐29b‐rich murine sEV were similarly obtained using mouse BMSCs and examined for in vivo effects with a syngeneic murine model using YTN16P, a highly metastatic clone of gastric cancer cell. Intraperitoneal (IP) transfer of the sEV every 3 days markedly reduced the number of PM from YTN16P in the mesentery (p < 0.05, n = 6) and the omentum (p < 0.05, n = 6). Bone marrow mesenchymal stem cell‐derived sEV are a useful carrier for IP administration of miR‐29b, which can suppress the development of PM of gastric cancer.
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spelling pubmed-103231012023-07-07 Intraperitoneal transfer of microRNA‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer Kimura, Yuki Ohzawa, Hideyuki Miyato, Hideyo Kaneko, Yuki Kuchimaru, Takahiro Takahashi, Rei Yamaguchi, Hironori Kurashina, Kentaro Saito, Shin Hosoya, Yoshinori Lefor, Alan Kawarai Sata, Naohiro Kitayama, Joji Cancer Sci ORIGINAL ARTICLES Small extracellular vesicles (sEV) contain various microRNAs (miRNAs) and play crucial roles in the tumor metastatic process. Although miR‐29b levels in peritoneal exosomes were markedly reduced in patients with peritoneal metastases (PM), their role has not been fully clarified. In this study, we asked whether the replacement of miR‐29b can affect the development of PM in a murine model. UE6E7T‐12, human bone marrow‐derived mesenchymal stem cells (BMSCs), were transfected with miR‐29b‐integrating recombinant lentiviral vector and sEV were isolated from culture supernatants using ultracentrifugation. The sEV contained markedly increased amounts of miR‐29b compared with negative controls. Treatment with transforming growth factor‐β1 decreased the expression of E‐cadherin and calretinin with increased expression of vimentin and fibronectin on human omental tissue‐derived mesothelial cells (HPMCs). However, the effects were totally abrogated by adding miR‐29b‐rich sEV. The sEV inhibited proliferation and migration of HPMCs by 15% (p < 0.005, n = 6) and 70% (p < 0.005, n = 6), respectively, and inhibited adhesion of NUGC‐4 and MKN45 to HPMCs by 90% (p < 0.0001, n = 5) and 77% (p < 0.0001, n = 5), respectively. MicroRNA‐29b‐rich murine sEV were similarly obtained using mouse BMSCs and examined for in vivo effects with a syngeneic murine model using YTN16P, a highly metastatic clone of gastric cancer cell. Intraperitoneal (IP) transfer of the sEV every 3 days markedly reduced the number of PM from YTN16P in the mesentery (p < 0.05, n = 6) and the omentum (p < 0.05, n = 6). Bone marrow mesenchymal stem cell‐derived sEV are a useful carrier for IP administration of miR‐29b, which can suppress the development of PM of gastric cancer. John Wiley and Sons Inc. 2023-04-03 /pmc/articles/PMC10323101/ /pubmed/36939028 http://dx.doi.org/10.1111/cas.15793 Text en © 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle ORIGINAL ARTICLES
Kimura, Yuki
Ohzawa, Hideyuki
Miyato, Hideyo
Kaneko, Yuki
Kuchimaru, Takahiro
Takahashi, Rei
Yamaguchi, Hironori
Kurashina, Kentaro
Saito, Shin
Hosoya, Yoshinori
Lefor, Alan Kawarai
Sata, Naohiro
Kitayama, Joji
Intraperitoneal transfer of microRNA‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer
title Intraperitoneal transfer of microRNA‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer
title_full Intraperitoneal transfer of microRNA‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer
title_fullStr Intraperitoneal transfer of microRNA‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer
title_full_unstemmed Intraperitoneal transfer of microRNA‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer
title_short Intraperitoneal transfer of microRNA‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer
title_sort intraperitoneal transfer of microrna‐29b‐containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer
topic ORIGINAL ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323101/
https://www.ncbi.nlm.nih.gov/pubmed/36939028
http://dx.doi.org/10.1111/cas.15793
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