• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Cell-to-cell communication between tumor cell and their microenvironment via exosomes

Research Project

Project/Area Number 25830089
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionTokyo Medical University

Principal Investigator

UMEZU Tomohiro  東京医科大学, 医学部, 講師 (40385547)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsがん微小環境 / エクソソーム / miRNA / 多発性骨髄腫 / 血管新生 / 低酸素環境 / 細胞間相互作用
Outline of Final Research Achievements

The aim of this study is to clarify the role of tumor-derived exosome in their microenvironment using multiple myeloma cell lines which show continuous growth in vitro under chronically hypoxic conditions (hypoxia-resistant MM cells; HR-MM cells). We isolated the exosomes from HR-MM cells and assessed exosomal miRNA profiling using the TaqMan low-density array. Endothelial tube formation assay was used for validating function of MM cell-endothelial cell (HUVECs) communication. We found miR-135b was significantly up-regulated in exosomes from HR-MM cells compared to those in the parental cells. The exosomal miR-135b directly suppressed its target, factor inhibiting HIF-1 (FIH-1), in endothelial cells, and enhanced endothelial tube formation under hypoxia. HR-MM cell-derived exosomes could enhance density of CD31 positive endothelial cells in Matrigel plug. Suggesting that the exosomal miR-135b might therefore be one of promising target for controlling angiogenesis in MM.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (12 results)

All 2014 2013 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (5 results) Remarks (2 results)

  • [Journal Article] Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1.2014

    • Author(s)
      Umezu T, Tadokoro H, Azuma K, Yoshizawa S, Ohyashiki K, Ohyashiki JH.
    • Journal Title

      Blood

      Volume: 124(25) Issue: 25 Pages: 3748-3757

    • DOI

      10.1182/blood-2014-05-576116

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Down-regulated microRNA-148b in circulating PBMCs in chronic myeloid leukemia patients with undetectable minimal residual disease: A possible molecular classifier to stop imatinib safely.2014

    • Author(s)
      Ohyashiki, J. H., Ohtsuki, K., Mizoguchi, I., Yoshimoto, T., Katagiri, S., Umezu, T., and Ohyashiki, K.
    • Journal Title

      Drug Des. Devel. Ther.

      Volume: 8 Pages: 1151-1159

    • DOI

      10.2147/dddt.s66812

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells.2013

    • Author(s)
      Tadokoro H, Umezu T, Ohyashiki K, Hirano T, and Ohyashiki JH.
    • Journal Title

      J. Biol. Chem

      Volume: 288 Issue: 48 Pages: 34343-34351

    • DOI

      10.1074/jbc.m113.480822

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical relevance of plasma miR-106b levels in patients with chronic obstructive pulmonary disease2013

    • Author(s)
      Soeda S, Ohyashiki JH, Ohtsuki K, Umezu T, Setoguchi Y, Ohyashiki K
    • Journal Title

      Int J Mol Med.

      Volume: 31(3) Issue: 3 Pages: 533-539

    • DOI

      10.3892/ijmm.2013.1251

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Leukemia cell to endothelial cell communication via exosomal miRNAs2013

    • Author(s)
      Umezu T, Ohyashiki K, Kuroda M, Ohyashiki JH
    • Journal Title

      Oncogene

      Volume: 32(22) Issue: 22 Pages: 2747-55

    • DOI

      10.1038/onc.2012.295

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] がん微小環境を制御するエクソソーム含有miRNA:長期低酸素曝露した骨髄腫細胞由来exosomal miR-135bの機能解析.2014

    • Author(s)
      Umezu T
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] がん微小環境ネットワークにおけるエクソソーム含有miRNAの機能解析2014

    • Author(s)
      梅津知宏
    • Organizer
      第8回エピジェネティクス研究会
    • Place of Presentation
      東京
    • Year and Date
      2014-05-25 – 2014-05-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Hypoxia enhances angiogenesis via exosomal miR-135b derived from multiple myeloma cells.2014

    • Author(s)
      Umezu T
    • Organizer
      International Society for Extracellular vesicles 2014
    • Place of Presentation
      Rotterdam, Netherland
    • Year and Date
      2014-04-11 – 2014-04-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Hypoxia modulates tumor exosomes, which function as mediators of angiogenesis.2013

    • Author(s)
      Umezu T
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington, DC, U. S. A.
    • Related Report
      2013 Research-status Report
  • [Presentation] Hypoxic myeloma cell modulates its microenvironment via exosomes2013

    • Author(s)
      梅津 知宏
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Remarks] 東京医科大学 医学総合研究所 分子腫瘍研究部門

    • URL

      http://team.tokyo-med.ac.jp/ims_onc/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京医科大学 医学総合研究所 分子腫瘍研究部門

    • URL

      http://team.tokyo-med.ac.jp/ims_onc/index.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi