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Understanding molecular mechanism underlying innate immune system escape for metastasis in sarcoma

Research Project

Project/Area Number 15K10458
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research Institution医療法人徳洲会野崎徳洲会病院(附属研究所) (2016-2017)
Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses (2015)

Principal Investigator

Sasagawa Satoru  医療法人徳洲会野崎徳洲会病院(附属研究所), 研究所, 部長 (80345115)

Research Collaborator ITOH Kazuyuki  医療法人徳洲会野崎徳洲会病院, 検診センター, センター長 (20301806)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords滑膜肉腫 / 転移 / 自然免疫応答 / 転移の分子メカニズム / Twist1
Outline of Final Research Achievements

In this study,we focused on the mechanism how the synovial sarcoma cells escape from immune surveillance and found that MICA/B molecules in synovial sarcoma cells were disappeared when the cells were in hypoxia and floating conditions. Twist1 transcription factor also depressed MICA/B expression. On the other hand, low-dose of HDAC inhibitors markedly up-regulated MICA/B expression. MICA/B expression was N-glycosylation sensitive and tunicamycin treatment rapidly killed MICA/B expression. We also found that MICA/B negative synovial sarcoma cells was also sensitive to HDAC inhibitor treatment and confirmed weak MICA/B protein expression. Here, we found that MICA/B mRNA sequence in MICA/B negative cells were not uniform and most of that disrupted N-glycosylation site in protein level. In conclusion, low-dose of HDAC inhibitor treatment could improve anti-tumor-effect by NK cells by MICA/B stimulation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2018 2017 2016 2015

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (2 results)

  • [Journal Article] Evidence for intrathecal sodium butyrate as a novel option for leptomeningeal metastasis.2018

    • Author(s)
      Nakagawa H, Yui Y, Sasagawa S, Itoh K.
    • Journal Title

      Journal of Neuro-Oncology

      Volume: 印刷中 Issue: 1 Pages: 43-50

    • DOI

      10.1007/s11060-018-2852-2

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sodium butyrate induces senescence and inhibits the invasiveness of glioblastoma cells.2018

    • Author(s)
      Nakagawa H, Sasagawa S, Itoh K.
    • Journal Title

      Oncology letter

      Volume: 15(2) Pages: 1495-1502

    • DOI

      10.3892/ol.2017.7518

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trabectedin is a promising antitumour agent for synovial sarcoma2016

    • Author(s)
      Yasui, H., Imura, Y., Outani, H., Hamada, K., Nakai, T., Yamada, S., Takenaka, S., Sasagawa, S., Araki, N., Itoh, K., Myoui, A., Yoshikawa, H., & Naka, N.
    • Journal Title

      Journal of Chemotherapy

      Volume: e-pub ahead of print Issue: 5 Pages: 1-8

    • DOI

      10.1080/1120009x.2015.1133013

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Trabectedin is a promising antitumour agent for synovial sarcoma2016

    • Author(s)
      Takaaki Nakai, Shutaro Yamada, Satoshi Takenaka, Satoru Sasagawa, Nobuhito Araki, Kazuyuki Itoh, Akira Myoui, Hideki Yoshikawa, Norifumi Naka
    • Journal Title

      Journal of Chemotherapy

      Volume: e-pub ahead of print

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Taspase1-dependent TFIIA cleavage coordinates head morphogenesis by limiting Cdkn2a locus transcription.2015

    • Author(s)
      Takeda S, Sasagawa S, Oyama T, Searleman AC, Westergard TD, Cheng EH, Hsieh JJ.
    • Journal Title

      The Journal of Clinical Investigation

      Volume: 125(3) Issue: 3 Pages: 1203-1214

    • DOI

      10.1172/jci77075

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Analysis of metastatic potential regulated by Twist1 in synovial sarcoma2017

    • Author(s)
      Satoru Sasagawa, Yoshihiro Yui, Kenta Watanabe, Hidemitsu Nakagawa, Kazuyuki Itoh.
    • Organizer
      日本癌学会 第76回学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Regulation of Metastatic Potential by Twist1 in Sarcoma2016

    • Author(s)
      S. Sasagawa, Y. Yui, H. Nakagawa, K. Itoh
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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