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Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells.
PLoS One 2013; 8(12):e84256Plos

Abstract

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.

Authors+Show Affiliations

Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea ; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea ; Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24391924

Citation

Lee, Jong-Kuen, et al. "Exosomes Derived From Mesenchymal Stem Cells Suppress Angiogenesis By Down-regulating VEGF Expression in Breast Cancer Cells." PloS One, vol. 8, no. 12, 2013, pp. e84256.
Lee JK, Park SR, Jung BK, et al. Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. PLoS ONE. 2013;8(12):e84256.
Lee, J. K., Park, S. R., Jung, B. K., Jeon, Y. K., Lee, Y. S., Kim, M. K., ... Kim, C. W. (2013). Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. PloS One, 8(12), pp. e84256. doi:10.1371/journal.pone.0084256.
Lee JK, et al. Exosomes Derived From Mesenchymal Stem Cells Suppress Angiogenesis By Down-regulating VEGF Expression in Breast Cancer Cells. PLoS ONE. 2013;8(12):e84256. PubMed PMID: 24391924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. AU - Lee,Jong-Kuen, AU - Park,Sae-Ra, AU - Jung,Bong-Kwang, AU - Jeon,Yoon-Kyung, AU - Lee,Yeong-Shin, AU - Kim,Min-Kyoung, AU - Kim,Yong-Goo, AU - Jang,Ji-Young, AU - Kim,Chul-Woo, Y1 - 2013/12/31/ PY - 2013/04/10/received PY - 2013/11/13/accepted PY - 2014/1/7/entrez PY - 2014/1/7/pubmed PY - 2014/9/3/medline SP - e84256 EP - e84256 JF - PloS one JO - PLoS ONE VL - 8 IS - 12 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24391924/Exosomes_derived_from_mesenchymal_stem_cells_suppress_angiogenesis_by_down_regulating_VEGF_expression_in_breast_cancer_cells_ L2 - http://dx.plos.org/10.1371/journal.pone.0084256 DB - PRIME DP - Unbound Medicine ER -