title: Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells.
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.affiliation: Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jong-Kuen
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Sae-Ra
authors.initials: SR
authors.lastname: Park
authors.affiliation: Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Bong-Kwang
authors.initials: BK
authors.lastname: Jung
authors.affiliation: 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.
authors.forename: Yoon-Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Yeong-Shin
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Yong-Goo
authors.initials: YG
authors.lastname: Kim
authors.affiliation: Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Jang
authors.affiliation: 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.
authors.forename: Chul-Woo
authors.initials: CW
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D059016:Tumor Microenvironment / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D035683:MicroRNAs; C522604:Mirn16 microRNA, mouse; D042461:Vascular Endothelial Growth Factor A