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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Veröffentlicht in:PloS one Jg. 8; H. 12; S. e84256
Hauptverfasser: Lee, Jong-Kuen, Park, Sae-Ra, Jung, Bong-Kwang, Jeon, Yoon-Kyung, Lee, Yeong-Shin, Kim, Min-Kyoung, Kim, Yong-Goo, Jang, Ji-Young, Kim, Chul-Woo
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 31.12.2013
Public Library of Science (PLoS)
Schlagworte:
Angiogenesis
Animals
Biology
Blotting, Western
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - physiopathology
Cancer
Cancer cells
Cell interactions
Cell Line, Tumor
Cell migration
Development and progression
DNA Primers - genetics
Enzyme-Linked Immunosorbent Assay
Exosomes
Exosomes - metabolism
Female
Gene Expression Regulation, Neoplastic - physiology
Hostages
Immunohistochemistry
Immunomodulation
In vivo methods and tests
Medical research
Medicine
Membrane vesicles
Mesenchymal stem cells
Mesenchymal Stem Cells - cytology
Mesenchyme
Mice
Mice, Inbred BALB C
MicroRNA
MicroRNAs - metabolism
miRNA
Neovascularization, Pathologic - metabolism
Paracrine signalling
Physicians
Real-Time Polymerase Chain Reaction
Ribonucleic acid
RNA
Stem cells
Tumor cells
Tumor Microenvironment - physiology
Tumors
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - metabolism
Vesicles
ISSN:1932-6203, 1932-6203
Online-Zugang:Volltext
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Zusammenfassung: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.
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Conceived and designed the experiments: JKL JYJ CWK. Performed the experiments: JKL SRP BKJ. Analyzed the data: JKL JYJ. Contributed reagents/materials/analysis tools: YSL MKK YGK. Wrote the paper: JKL YKJ JYJ.
Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0084256