アズマ ケンコウ
  東 剣虹
   所属   研究施設 研究施設
   職種   助教
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1.
掲載誌名 正式名:Blood
略  称:Blood
ISSNコード:(1528-0020)0006-4971(Linking)
巻・号・頁 124(25),pp.3748-57
著者・共著者 Umezu Tomohiro, Tadokoro Hiroko, Azuma Kenko, Yoshizawa Seiichiro, Ohyashiki Kazuma, Ohyashiki Junko H
発行年月 2014/12
概要 Exosomes are small endosome-derived vesicles containing a wide range of functional proteins, mRNA, and miRNA. Exosomal miRNA from cancer cells helps modulate the microenvironment. In multiple myeloma (MM), the massive proliferation of malignant plasma cells causes hypoxia. To date, the majority of in vitro hypoxia studies of cancer cells have used acute hypoxic exposure (3-24 hours). Thus, we attempted to clarify the role of MM-derived exosomes in hypoxic bone marrow by using MM cells grown continuously in vitro under chronic hypoxia (hypoxia-resistant MM [HR-MM] cells). The HR-MM cells produced more exosomes than the parental cells under normoxia or acute hypoxia conditions, and miR-135b was significantly upregulated in exosomes from HR-MM cells. Exosomal miR-135b directly suppressed its target factor-inhibiting hypoxia-inducible factor 1 (FIH-1) in endothelial cells. Finally, exosomal miR-135b from HR-MM cells enhanced endothelial tube formation under hypoxia via the HIF-FIH signaling pathway. This in vitro HR myeloma cell model will be useful for investigating MM cell-endothelial cell interactions under hypoxic conditions, which may mimic the in vivo bone marrow microenvironment. Although tumor angiogenesis is regulated by various factors, exosomal miR-135b may be a target for controlling MM angiogenesis.
DOI 10.1182/blood-2014-05-576116
PMID 25320245