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A Small Vimentin-Binding Molecule Blocks Cancer Exosome Release and Reduces Cancer Cell Mobility

Vimentin is an intermediate filament protein with diverse roles in health and disease far beyond its structural functions. Exosomes or small extracellular vesicles (sEVs) are key mediators for intercellular communication, contributing to tissue homeostasis and the progression of various diseases, es...

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Autores principales: Wu, Jianping, Xie, Qian, Liu, Yanjun, Gao, Yanan, Qu, Zhipeng, Mo, Lian, Xu, Ying, Chen, Ruihuan, Shi, Liyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297618/
https://www.ncbi.nlm.nih.gov/pubmed/34305581
http://dx.doi.org/10.3389/fphar.2021.627394
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author Wu, Jianping
Xie, Qian
Liu, Yanjun
Gao, Yanan
Qu, Zhipeng
Mo, Lian
Xu, Ying
Chen, Ruihuan
Shi, Liyun
author_facet Wu, Jianping
Xie, Qian
Liu, Yanjun
Gao, Yanan
Qu, Zhipeng
Mo, Lian
Xu, Ying
Chen, Ruihuan
Shi, Liyun
author_sort Wu, Jianping
collection PubMed
description Vimentin is an intermediate filament protein with diverse roles in health and disease far beyond its structural functions. Exosomes or small extracellular vesicles (sEVs) are key mediators for intercellular communication, contributing to tissue homeostasis and the progression of various diseases, especially the metastasis of cancers. In this study, we evaluated a novel vimentin-binding compound (R491) for its anti-cancer activities and its roles in cancer exosome release. The compound R491 induced a rapid and reversible intracellular vacuolization in various types of cancer cells. This phenotype did not result in an inhibition of cancer cell growth, which was consistent with our finding from a protein array that R491 did not reduce levels of major oncoproteins in cancer cells. Morphological and quantitative analyses on the intracellular vacuoles and extracellular exosomes revealed that in response to R491 treatment, the exosomes released from the cells were significantly reduced, while the exosomes retained as intra-luminal vesicles inside the cells were subsequently degraded. Vim(+/−) cells had lower amounts of vimentin and accordingly, lower amounts of both the retained and the released exosomes than Vim(+/+) cells had, while the vimentin-binding compound R491 inhibited only the release of exosomes. Further functional tests showed that R491 significantly reduced the migration and invasion of cancer cells in vitro and decreased the amount of exosome in the blood in mice. Our study suggests that vimentin promotes exosome release, and small-molecule compounds that target vimentin are able to both block cancer exosome release and reduce cancer cell motility, and therefore could have potential applications for inhibiting cancer invasive growth.
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spelling pubmed-82976182021-07-23 A Small Vimentin-Binding Molecule Blocks Cancer Exosome Release and Reduces Cancer Cell Mobility Wu, Jianping Xie, Qian Liu, Yanjun Gao, Yanan Qu, Zhipeng Mo, Lian Xu, Ying Chen, Ruihuan Shi, Liyun Front Pharmacol Pharmacology Vimentin is an intermediate filament protein with diverse roles in health and disease far beyond its structural functions. Exosomes or small extracellular vesicles (sEVs) are key mediators for intercellular communication, contributing to tissue homeostasis and the progression of various diseases, especially the metastasis of cancers. In this study, we evaluated a novel vimentin-binding compound (R491) for its anti-cancer activities and its roles in cancer exosome release. The compound R491 induced a rapid and reversible intracellular vacuolization in various types of cancer cells. This phenotype did not result in an inhibition of cancer cell growth, which was consistent with our finding from a protein array that R491 did not reduce levels of major oncoproteins in cancer cells. Morphological and quantitative analyses on the intracellular vacuoles and extracellular exosomes revealed that in response to R491 treatment, the exosomes released from the cells were significantly reduced, while the exosomes retained as intra-luminal vesicles inside the cells were subsequently degraded. Vim(+/−) cells had lower amounts of vimentin and accordingly, lower amounts of both the retained and the released exosomes than Vim(+/+) cells had, while the vimentin-binding compound R491 inhibited only the release of exosomes. Further functional tests showed that R491 significantly reduced the migration and invasion of cancer cells in vitro and decreased the amount of exosome in the blood in mice. Our study suggests that vimentin promotes exosome release, and small-molecule compounds that target vimentin are able to both block cancer exosome release and reduce cancer cell motility, and therefore could have potential applications for inhibiting cancer invasive growth. Frontiers Media S.A. 2021-07-08 /pmc/articles/PMC8297618/ /pubmed/34305581 http://dx.doi.org/10.3389/fphar.2021.627394 Text en Copyright © 2021 Wu, Xie, Liu, Gao, Qu, Mo, Xu, Chen and Shi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wu, Jianping
Xie, Qian
Liu, Yanjun
Gao, Yanan
Qu, Zhipeng
Mo, Lian
Xu, Ying
Chen, Ruihuan
Shi, Liyun
A Small Vimentin-Binding Molecule Blocks Cancer Exosome Release and Reduces Cancer Cell Mobility
title A Small Vimentin-Binding Molecule Blocks Cancer Exosome Release and Reduces Cancer Cell Mobility
title_full A Small Vimentin-Binding Molecule Blocks Cancer Exosome Release and Reduces Cancer Cell Mobility
title_fullStr A Small Vimentin-Binding Molecule Blocks Cancer Exosome Release and Reduces Cancer Cell Mobility
title_full_unstemmed A Small Vimentin-Binding Molecule Blocks Cancer Exosome Release and Reduces Cancer Cell Mobility
title_short A Small Vimentin-Binding Molecule Blocks Cancer Exosome Release and Reduces Cancer Cell Mobility
title_sort small vimentin-binding molecule blocks cancer exosome release and reduces cancer cell mobility
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297618/
https://www.ncbi.nlm.nih.gov/pubmed/34305581
http://dx.doi.org/10.3389/fphar.2021.627394
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