title: Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells.
abstract: Hypoxia plays an important role during the evolution of cancer cells and their microenvironment. Emerging evidence suggests communication between cancer cells and their microenvironment occurs via exosomes. This study aimed to clarify whether hypoxia affects angiogenic function through exosomes secreted from leukemia cells. We used the human leukemia cell line K562 for exosome-generating cells and human umbilical vein endothelial cells (HUVECs) for exosome target cells. Exosomes derived from K562 cells cultured under normoxic (20%) or hypoxic (1%) conditions for 24 h were isolated and quantitated by nanoparticle tracking analysis. These exosomes were then cocultured with HUVECs to evaluate angiogenic activity. The exosomes secreted from K562 cells in hypoxic conditions significantly enhanced tube formation by HUVECs compared with exosomes produced in normoxic conditions. Using a TaqMan low-density miRNA array, we found a subset of miRNAs, including miR-210, were significantly increased in exosomes secreted from hypoxic K562 cells. We demonstrated that cancer cells and their exosomes have altered miRNA profiles under hypoxic conditions. Although exosomes contain various molecular constituents such as proteins and mRNAs, altered exosomal compartments under hypoxic conditions, including miR-210, affected the behavior of endothelial cells. Our results suggest that exosomal miRNA derived from cancer cells under hypoxic conditions may partly affect angiogenic activity in endothelial cells.
authors.affiliation: From the Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Science, Tokyo 192-0392, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tadokoro
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Umezu
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
authors.forename: Junko H
authors.initials: JH
authors.lastname: Ohyashiki
mesh_terms: D015687:Cell Hypoxia; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism
chemical_list: C543800:MIRN210 microRNA, human; D035683:MicroRNAs
keywords: Angiogenesis; Cell-cell Interaction; Exosomes; Hypoxia; MicroRNA