Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells.

Exosomes are small membrane vesicles released by a variety of cell types. Exosomes contain genetic materials, such as mRNAs and microRNAs (miRNAs), implying that they may play a pivotal role in cell-to-cell communication. Mesenchymal stem cells (MSCs), which potentially differentiate into multiple c...

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Autores principales: Jong-Kuen Lee, Sae-Ra Park, Bong-Kwang Jung, Yoon-Kyung Jeon, Yeong-Shin Lee, Min-Kyoung Kim, Yong-Goo Kim, Ji-Young Jang, Chul-Woo Kim
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/8ceb237d356d41229cc803dd4133d56d
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spelling oai:doaj.org-article:8ceb237d356d41229cc803dd4133d56d2021-11-18T08:39:22ZExosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells.1932-620310.1371/journal.pone.0084256https://doaj.org/article/8ceb237d356d41229cc803dd4133d56d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24391924/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Exosomes are small membrane vesicles released by a variety of cell types. Exosomes contain genetic materials, such as mRNAs and microRNAs (miRNAs), implying that they may play a pivotal role in cell-to-cell communication. Mesenchymal stem cells (MSCs), which potentially differentiate into multiple cell types, can migrate to the tumor sites and have been reported to exert complex effects on tumor progression. To elucidate the role of MSCs within the tumor microenvironment, previous studies have suggested various mechanisms such as immune modulation and secreted factors of MSCs. However, the paracrine effects of MSC-derived exosomes on the tumor microenvironment remain to be explored. The hypothesis of this study was that MSC-derived exosomes might reprogram tumor behavior by transferring their molecular contents. To test this hypothesis, exosomes from MSCs were isolated and characterized. MSC-derived exosomes exhibited different protein and RNA profiles compared with their donor cells and these vesicles could be internalized by breast cancer cells. The results demonstrated that MSC-derived exosomes significantly down-regulated the expression of vascular endothelial growth factor (VEGF) in tumor cells, which lead to inhibition of angiogenesis in vitro and in vivo. Additionally, miR-16, a miRNA known to target VEGF, was enriched in MSC-derived exosomes and it was partially responsible for the anti-angiogenic effect of MSC-derived exosomes. The collective results suggest that MSC-derived exosomes may serve as a significant mediator of cell-to-cell communication within the tumor microenvironment and suppress angiogenesis by transferring anti-angiogenic molecules.Jong-Kuen LeeSae-Ra ParkBong-Kwang JungYoon-Kyung JeonYeong-Shin LeeMin-Kyoung KimYong-Goo KimJi-Young JangChul-Woo KimPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e84256 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jong-Kuen Lee
Sae-Ra Park
Bong-Kwang Jung
Yoon-Kyung Jeon
Yeong-Shin Lee
Min-Kyoung Kim
Yong-Goo Kim
Ji-Young Jang
Chul-Woo Kim
Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells.
description Exosomes are small membrane vesicles released by a variety of cell types. Exosomes contain genetic materials, such as mRNAs and microRNAs (miRNAs), implying that they may play a pivotal role in cell-to-cell communication. Mesenchymal stem cells (MSCs), which potentially differentiate into multiple cell types, can migrate to the tumor sites and have been reported to exert complex effects on tumor progression. To elucidate the role of MSCs within the tumor microenvironment, previous studies have suggested various mechanisms such as immune modulation and secreted factors of MSCs. However, the paracrine effects of MSC-derived exosomes on the tumor microenvironment remain to be explored. The hypothesis of this study was that MSC-derived exosomes might reprogram tumor behavior by transferring their molecular contents. To test this hypothesis, exosomes from MSCs were isolated and characterized. MSC-derived exosomes exhibited different protein and RNA profiles compared with their donor cells and these vesicles could be internalized by breast cancer cells. The results demonstrated that MSC-derived exosomes significantly down-regulated the expression of vascular endothelial growth factor (VEGF) in tumor cells, which lead to inhibition of angiogenesis in vitro and in vivo. Additionally, miR-16, a miRNA known to target VEGF, was enriched in MSC-derived exosomes and it was partially responsible for the anti-angiogenic effect of MSC-derived exosomes. The collective results suggest that MSC-derived exosomes may serve as a significant mediator of cell-to-cell communication within the tumor microenvironment and suppress angiogenesis by transferring anti-angiogenic molecules.
format article
author Jong-Kuen Lee
Sae-Ra Park
Bong-Kwang Jung
Yoon-Kyung Jeon
Yeong-Shin Lee
Min-Kyoung Kim
Yong-Goo Kim
Ji-Young Jang
Chul-Woo Kim
author_facet Jong-Kuen Lee
Sae-Ra Park
Bong-Kwang Jung
Yoon-Kyung Jeon
Yeong-Shin Lee
Min-Kyoung Kim
Yong-Goo Kim
Ji-Young Jang
Chul-Woo Kim
author_sort Jong-Kuen Lee
title Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells.
title_short Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells.
title_full Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells.
title_fullStr Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells.
title_full_unstemmed Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells.
title_sort exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating vegf expression in breast cancer cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/8ceb237d356d41229cc803dd4133d56d
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