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Sialoglycan facilitate cancer escape from immunosurveillance via sialic acid-binding Siglec-7 on NK cells

Research Project

Project/Area Number 26860320
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Immunology
Research InstitutionNagoya University

Principal Investigator

Hashimoto Noboru  名古屋大学, 医学(系)研究科(研究院), 研究機関研究員 (90712365)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords糖鎖 / 癌 / 免疫 / 免疫監視機構 / 質量分析 / シアル酸
Outline of Final Research Achievements

Siglec-7 is an inhibitory receptor expressed on NK cells and monocytes and transduces inhibitory signals into immune cells by binding to its ligands. Although a few ligands have been reported, specificity of Siglec-7-recognized structures has not been clarified. To solve this issue, we established several sialyltransferase-transfectants that showed definite binding of Siglec-7-Fc using a human colon cancer cell line. By using the transfectants, we clarified o-glycan is a new ligand of Siglec-7. While NK cells showed high cytotoxic activity toward the parent cells, reduced cytotoxicity was observed for the transfectants. In addition, ITIM of Siglec-7 was strongly phosphorylated in the transfectants. As for the transfectants, Siglec-7-binding enhanced cell migration. Taken together, we suggest that interaction between Siglec-7 and O-glycan enable cancer cells to escape from immunosurveillance by suppression of immune cells and enhancement of cancer malignancy.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (14 results)

All 2016 2015 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 1 results) Book (2 results)

  • [Journal Article] Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Promote Recovery after Rat Spinal Cord Injury by Altering Macrophage Polarity2015

    • Author(s)
      Kohki Matsubara, Yoshihiro Matsushita, Kiyoshi Sakai, Fumiya Kano, Megumi Kondo, Mariko Noda, Noboru Hashimoto, Shiro Imagama, Naoki Ishiguro, Akio Suzumura, Minoru Ueda, Koichi Furukawa, Akihito Yamamoto
    • Journal Title

      Journal of Neuroscience

      Volume: 35 Issue: 6 Pages: 2452-2464

    • DOI

      10.1523/jneurosci.4088-14.2015

    • NAID

      120005946848

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Structuralspecificity in molecular recognition of Siglec-7 to ganglooside GD32016

    • Author(s)
      Noboru Hashimoto, Sizuka Ito,Kazutaka Ikeda, Akiko Tsuchida, Paul R. Crocker, Keiko Furukawa, Ryo Taguchi, Koichi Furukawa
    • Organizer
      Gordom Research Conference-Glycolipid & Sphingolipid Biology
    • Place of Presentation
      Lucca (Barga), Italy
    • Year and Date
      2016-03-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TLC-LESA-QTRAP6500によるSiglec-7特異的認識ganglioside GD3の構造解析2015

    • Author(s)
      橋本登、伊藤静、池田和貴、土田明子、Paul R. Crocker、古川圭子、田口良、古川鋼一
    • Organizer
      BMB2015
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] Sialo-O-glycan facilitate cancer escape from immunosurveillance via sialic acid-binding Siglec-7 on NK cells2015

    • Author(s)
      橋本登、土田明子、高野舞子、古川圭子、古川鋼一
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Sialo-O-glycan facilitate cancer escape from immunosurveillance via sialic acid-binding Siglec-7 on NK cells2015

    • Author(s)
      Noboru Hashimoto, Akiko Tsuchida, Maiko Takano, Keiko Furukawa, Koichi Furukawa
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場、愛知県、名古屋
    • Year and Date
      2015-10-08 – 2015-10-10
    • Related Report
      2014 Research-status Report
  • [Presentation] Siglec-7の結合特異性におけるガングリオシドGD3の分子種解析2015

    • Author(s)
      橋本登、伊藤静、池田和貴、土田明子、Paul R. Crocker、古川圭子、田口良、古川鋼一
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] TLC-LESA-QTRAP6500によるSiglec-7認識ganglioside GD3の構造解析2015

    • Author(s)
      橋本登、伊藤静、池田和貴、土田明子、Paul R. Crocker、古川圭子、田口良、古川鋼一
    • Organizer
      The 42nd Biological Mass Spectrometry Conference
    • Place of Presentation
      岐阜グランドホテル(岐阜県岐阜市)
    • Year and Date
      2015-07-07
    • Related Report
      2015 Annual Research Report
  • [Presentation] Siglec-7とガングリオシドGD3の結合における分子認識の構造特異性2014

    • Author(s)
      橋本 登、伊藤 静香、水野 顕智、池田 和貴、土田 明子、Paul R. Crocker、古川 圭子、田口 良、古川 鋼一
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜、神奈川県、横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Proteomic analysis of ganglioside-associated microdomain in malignant melanomas.2014

    • Author(s)
      Noboru Hashimoto, Kazunori Hamamura, Norihiro Kotani, Keiko Furukawa, Kei Kaneko, Koichi Honke, Koichi Furukawa
    • Organizer
      SFG & JSCR 2014 Joint Annual Meeting
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2014-11-16 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] Modulation of malignant properties of cancer cells by binding of a sialic acid-recognizing lectin Siglec-9 via calpain-mediated degradation of focal adhesion kinase and related proteins.2014

    • Author(s)
      Koichi Furukawa, Yilihamujiang Shabiti, Noboru Hashimoto, Yasuyuki Matsumoto, Toshiyuki Yamaji, Keiko Furukawa
    • Organizer
      SFG & JSCR 2014 Joint Annual Meeting
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2014-11-16 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] Binding of a sialic acid-recognizing lectin Siglec-9 modulates malignant properties of cancer cells via calpain-mediated degradation of focal adhesion kinase and related proteins.2014

    • Author(s)
      Koichi Furukawa, Ilhamjan Sabit, Noboru Hashimoto, Yasuyuki Matsumoto, Toshiyuki Yamaji, Keiko Furukawa
    • Organizer
      SIALOGLYCO2014
    • Place of Presentation
      Gold Coast, Australia
    • Year and Date
      2014-09-07 – 2014-09-10
    • Related Report
      2014 Research-status Report
  • [Presentation] スフィンゴ糖脂質機能の統合的理解2014

    • Author(s)
      古川鋼一、橋本 登、大川祐樹、大海雄介、金子 慶、古川圭子
    • Organizer
      33回日本糖質学会年会
    • Place of Presentation
      名古屋大学、愛知県、名古屋
    • Year and Date
      2014-08-10 – 2014-08-12
    • Related Report
      2014 Research-status Report
  • [Book] The role of glycosphingolipids in lipid rafts: lessons from knockout mice. In Lipid Rafts: Properties, controversies and roles in signal transduction.2014

    • Author(s)
      Koichi Furukawa, Yusuke Ohmi, Yuji Kondo, Yuki Ohkawa, Noboru Hashimoto, Orie Tajima, Keiko Furukawa
    • Total Pages
      270
    • Publisher
      Nova Science Publishers
    • Related Report
      2014 Research-status Report
  • [Book] Gangliosides, synthesis and function in nervous tissue. In Glycoscience: Biology and Medicine2014

    • Author(s)
      Koichi Furukawa, Yusuke Ohmi, Yuki Ohkawa, Noboru Hashimoto, Yoshio Yamauchi, Orie Tajima, Keiko Furukawa
    • Total Pages
      1569
    • Publisher
      Springer
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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