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Mechanisms for innate immune check-point generated by siglecs and sialic acid-containing carbohydrates

Research Project

Project/Area Number 15K15080
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionChubu University

Principal Investigator

FURUKAWA Koichi  中部大学, 生命健康科学部, 教授 (80211530)

Co-Investigator(Kenkyū-buntansha) 山内 祥生  東京大学, 大学院農学生命科学研究科(農学部), 特任准教授 (00444878)
橋本 登  徳島大学, 大学院医歯薬学研究部(歯学系), 助教 (90712365)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsシグレック / 自然免疫 / シアル酸 / チェックポイント / 癌免疫 / 糖鎖 / 細胞傷害 / 糖脂質 / シグナル / 単球 / マクロファージ / アストロサイトーマ
Outline of Final Research Achievements

Sialic acid-containing cancer-associated carbohydrates are involved in the malignant properties of tumor cells, while innate immune cells such as NK and monocyte-macrophages express sialic-acid-recognizing lectins such as siglec-7 and 9. Then, significance and application for therapeutics of their interaction have been analyzed.
Analyses of carbohydrate structures recognized by siglecs and of their carrier molecules were performed, showing that siglec-7 recognized disialyl glycolipids such as GD3, and tri-sialylated carbohydrate-conjugated proteins. It was also shown that signals mediated by siglec-7 suppressed NK activity. Furthermore, it was demonstrated that GD3 with hydroxylated long chain base at C4 was not recognized by siglec-7, and also glycolipids containing hydroxylated ceramides scarcely localized in lipid rafts.

Report

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

    (24 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 6 results,  Acknowledgement Compliant: 5 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Book (3 results)

  • [Int'l Joint Research] Dundee University(英国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] ASC amino acid transporter 2, defined by enzyme-mediated activation of radical sources, enhances malignancy of GD2-positive small-cell lung cancer.2018

    • Author(s)
      Nobutoshi Esaki, Yuki Ohkawa, Noboru Hashimoto, Yuhsuke Tsuda, Yuhsuke Ohmi, Robiul H. Bhuiyan, Norihiro Kotani, Koichi Honke, Atsushi Enomoto, Masahide Takahashi, Keiko Furukawa, Koichi Furukawa.
    • Journal Title

      Cancer sci.

      Volume: 109 Issue: 1 Pages: 141-153

    • DOI

      10.1111/cas.13448

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycolipids: Essential regulator of neuro-inflammation, metabolism and gliomagenesis.2017

    • Author(s)
      Koichi Furukawa, Yuhsuke Ohmi, Shuting Ji, Pu Zhang, Robiul H. Bhuiyan, Yuki Ohkawa, Orie Tajima, Noboru Hashimoto, Keiko Furukawa
    • Journal Title

      Biochim. Biophys. Acta

      Volume: 1861 Issue: 10 Pages: 2479-2484

    • DOI

      10.1016/j.bbagen.2017.06.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional characterization of a novel GFI1B mutation causing congenital macrothrombocytopenia2016

    • Author(s)
      Bhuiyan RH, Yuji Kondo, Noriyo Tokuda, Ryota Mori, Keiko Furukawa, Koichi Furukawa
    • Journal Title

      Glycobiology

      Volume: 26 Pages: 984-998

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis.2016

    • Author(s)
      Ishikawa J, Takahashi N, Matsumoto T, Yoshioka Y, Yamamoto N, Nishikawa M, Hibi H, Ishigro N, Ueda M, Furukawa K, Yamamoto A.
    • Journal Title

      Bone.

      Volume: 83 Pages: 210-219

    • DOI

      10.1016/j.bone.2015.11.012

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Expression of B4GALNT1, an essential glycosyltransferase for the synthesis of complex gangliosides, suppresses BACE1 degradation and modulates APP processing2016

    • Author(s)
      Yamaguchi T, Yamauchi Y, Furukawa K, Ohmi Y, Ohkawa Y, Zhang Q, Okajima T, Furukawa K
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 34505-34505

    • DOI

      10.1038/srep34505

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Soluble Siglec-9 suppresses arthritis in a collagen-induced arthritis mouse model and inhibits M1 activation of RAW264.7 macrophages.2016

    • Author(s)
      Matsumoto T, Takahashi N, Kojima T, Yoshioka Y, Ishikawa J, Furukawa K, Ono K, Sawada M, Ishiguro N, Yamamoto A.
    • Journal Title

      Arthritis Research & Therapy

      Volume: 18(1) Issue: 1 Pages: 133-133

    • DOI

      10.1186/s13075-016-1035-9

    • NAID

      120006937643

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Ganglioside GD3 enhances invasiveness via Yes activation by forming a complex of GD3/PDGFRα/Yes in gliomas2015

    • Author(s)
      Yuki Ohkawa, Hiroyuki Momota, Akira Kato, Noboru Hashimoto, Yuhsuke Tsuda, Norihiro Kotani, Koichi Honke, Akio Suzumura, Keiko Furukawa, Yuhsuke Ohmi, Atsushi Natsume, Toshihiko Wakabayashi and *Furukawa K
    • Journal Title

      J. Biol. Chem.

      Volume: 290 Issue: 32 Pages: 16043-16058

    • DOI

      10.1074/jbc.m115.708834

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Regulatory function of glycosphingolipids in the inflammation and degeneration.2015

    • Author(s)
      Furukawa K., Ohmi Y., Kondo Y., Ohkawa Y., Tajima O. and Furukawa K
    • Journal Title

      Arch Biochem Biophys

      Volume: 571 Pages: 58-65

    • DOI

      10.1016/j.abb.2015.02.007

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Akt-girdin signaling in cancer-associated fibroblasts contributes to tumor progression2015

    • Author(s)
      Yumiko Yamamura, Naoya Asai, Atsushi Enomoto, Takuya Kato, Shinji Mii, Yuji Kondo, Kaori Ushida, Kaoru Niimi, Nobuyuki Tsunoda, Masato Nagino, Shu Ichihara, Koichi Furukawa, Kengo Maeda, Toyoaki Murohara, Masahide Takahashi
    • Journal Title

      Cancer Research

      Volume: 75 Issue: 5 Pages: 813-823

    • DOI

      10.1158/0008-5472.can-14-1317

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Regulation of cell signaling by ganglioside GD3/GD2 in gliomas2017

    • Author(s)
      Koichi Furukawa, Yuki Ohkawa, Kei Kaneko, Noboru Hashimoto, Zhang Pu, Robiul H. Bhuiyan, Yuhsuke Ohmi, Keiko Furukawa
    • Organizer
      GLYCO XXIV
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 癌関連糖脂質GD3とSiglec-7による腫瘍免疫監視逃避機構の解明2016

    • Author(s)
      橋本 登, 伊藤静香, 池田和貴, 土田明子, Paul R. Crocker, 古川圭子, 田口 良, 古川鋼一
    • Organizer
      第39回 日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
  • [Presentation] グリオーマにおいてGD3発現に伴って発現する遺伝子群の同定2016

    • Author(s)
      大川祐樹, 野田誠也, 百田洋之, 加藤 彰, 張 璞, 古川圭子, 大海雄介, 夏目敦至, 若林俊彦, 古川鋼一
    • Organizer
      第75回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] GD3-expressing glioma reduce M1-like phenotypes of glioma-associated microglia/macrophages via inflammatory cytokines2016

    • Author(s)
      張 璞, 大川祐樹, RH. Bhuiyan, 大海雄介, 高野舞子, 古川圭子, 古川鋼一
    • Organizer
      第75回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] TNFαとcAMPはメラノサイトにおいてメラノーマ関連糖鎖合成酵素遺伝子の発現を分別的に制御する2016

    • Author(s)
      竹内理香, 宮田麻衣子, ウプル ジャヤデワン, 田島織絵, 神戸真理子, 古川 鋼一, 古川圭子
    • Organizer
      第75回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] 癌関連スフィンゴ糖脂質糖鎖による細胞形質の制御2016

    • Author(s)
      古川圭子, 神戸真理子, 大川祐樹, 大海雄介, 竹内理香, 田島織絵, 古川鋼一
    • Organizer
      第89回 日本生化学会大会
    • Place of Presentation
      仙台国際センター・東北大川内北キャンパス(宮城県仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] グリオーマにおいてガングリオシドGD3はPDGFRαの発現を誘導する2016

    • Author(s)
      大川祐樹, 百田洋之, 加藤 彰, 橋本 登, 古川圭子, 大海雄介, 夏目敦至, 若林 俊彦, 古川鋼一
    • Organizer
      第35回 日本糖質学会年会
    • Place of Presentation
      文化プラザかるぽーと(高知県高知市)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
  • [Presentation] GD3は炎症性サイトカインを介してグリオーマ関連ミクログリアのM1様表現型を抑制する2016

    • Author(s)
      張 璞, 大川祐樹, Bhuiyan RH, 百田洋介, 若林俊彦, 大海雄介, 古川圭子, 岡島徹也. 古川鋼一
    • Organizer
      第35回 日本糖質学会年会
    • Place of Presentation
      文化プラザかるぽーと(高知県高知市)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
  • [Presentation] 糖脂質糖鎖によるシグナルの制御のメカニズム2015

    • Author(s)
      古川鋼一、大川祐樹、大海雄介、橋本登、古川圭子
    • Organizer
      第38回 日本分子生物学会年会 第88回 日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Gene expression analysis in mouse RAW264-7cells treated with Siglec-9 and MCP-12015

    • Author(s)
      TAKANO Maiko,HASIMOTO Nboru,OHKAWA Yuki ,MATUBARA Kohki,YAMAMOTO Akiko,FURUKAWA Keiko,FURUKAWA Koichi
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Novel functions and mechanisms of complex carbo-hydrates elucidated by glycosyltransferase gene knockout2015

    • Author(s)
      Koichi Furukawa
    • Organizer
      GLYCO23(第23回 国際糖鎖学会
    • Place of Presentation
      クロアチア、スプリット
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] Glyco-signals in Cancer2016

    • Author(s)
      Koichi Furukawa, Yuki Ohkawa, Yasuyuki Matsumoto, Yuhsuke Ohmi, Noboru Hashimoto, Keiko Furukawa Regulatory Mechanisms for Malignant Properties of Cancer Cells with Disialyl and Monosialyl Gangliosides
    • Publisher
      Springer
    • Related Report
      2016 Research-status Report
  • [Book] Lipid/rafts2016

    • Author(s)
      Koichi Furukawa, Yuhsuke Ohmi, Yuki Ohkawa, Noboru Hashimoto, Yuji Kondo, Orie Tajima, Keiko Furukawa
    • Publisher
      Nova Science Publishers
    • Related Report
      2016 Research-status Report
  • [Book] Gangliosides Regulate Tumor Properties: With Focus on the Suppression of Metastasis-Associated ppGalNAc-T13 with GM1. In Sugar Chains2015

    • Author(s)
      Koichi Furukawa, Yasuyuki Matsumoto, Qing Zhang, and Keiko Furukawa
    • Total Pages
      288
    • Publisher
      Springer
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-02-21  

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