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Development of molecular-targeted therapeutic agent targeting novel platelet activation receptor CLEC-2

Research Project

Project/Area Number 15K19549
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionUniversity of Yamanashi

Principal Investigator

SASAKI Tomoyuki  山梨大学, 総合研究部, 助教 (40739124)

Research Collaborator SHIRAI Toshiaki  
TSUKIJI Nagaharu  
SHINMORI Hedeyuki  
INOUE Katsue  
OZAKI Yukio  
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords血小板 / CLEC-2 / ロドサイチン
Outline of Final Research Achievements

Platelet activation receptor CLEC-2 binds to podoplanin expressed on the surface of several kinds of cancer cells, which facilitates cancer metastasis. Therefore, anti-CLEC-2 drugs are expected to have anti-platelet and anti-metastatic effects. We focused on snake venom rhodocytin as its drug discovery source. In order to verify the binding site of rhodocytin with CLEC-2 and the formation mechanism of the complex, recombinant wild-type and mutant rhodocytin were produced with mammalian cell line. As a result, we found mutant rhodocytin with anti-CLEC-2 effect. In the mouse model, this mutant rhodocytin strongly inhibited podoplanin-dependent cancer metastasis without inducing platelet aggregation.

Report

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

    (17 results)

All 2017 2016 2015 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (11 results) (of which Int'l Joint Research: 3 results) Remarks (1 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Journal Article] CLEC-2 promotes hematogenous tumor metastasis and prothrombotic state in tumor-bearing mice.2016

    • Author(s)
      Shirai, Toshiaki Inoue, Osamu Tamura, Shogo Tsukiji, Nagaharu Sasaki, Tomoyuki Endo, Hiroshi Satoh, Kaneo Osada, Makoto Sato-Uchida, Hitomi Fujii, Hideki Ozaki, Yukio Suzuki-Inoue, Katsue
    • Journal Title

      Journal of thrombosis and haemostasis

      Volume: 38 Issue: 3 Pages: 42-49

    • DOI

      10.1111/jth.13604

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Podoplanin-positive periarteriolar stromal cells promote megakaryocyte growth and proplatelet formation in mice by CLEC-22016

    • Author(s)
      TAMURA Shogo, SUZUKI-INOUE Katsue, TSUKIJI Nagaharu, SHIRAI Toshiaki, SASAKI Tomoyuki, OSADA Makoto, SATOH Kaneo, OZAKI Yukio
    • Journal Title

      Blood

      Volume: 127 Issue: 13 Pages: 1701-1710

    • DOI

      10.1182/blood-2015-08-663708

    • NAID

      130007432250

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 変異型ロドサイチンによるポドプラニン依存性の癌細胞血行性転移の抑制2016

    • Author(s)
      佐々木知幸, 白井俊光, 築地長治, 田村彰吾, 長田誠, 佐藤金夫, 尾崎由基男, 井上克枝
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター(宮城・仙台)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 遺伝子組換えロドサイチンを用いたCLEC-2依存性血小板凝集の制御解析2016

    • Author(s)
      佐々木知幸,白井俊光,築地長治,田村彰吾,長田誠,佐藤金夫,尾崎由基男,井上克枝
    • Organizer
      第38回日本血栓止血学会学術集会
    • Place of Presentation
      奈良春日野国際フォーラム(奈良・奈良)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report 2015 Research-status Report
  • [Presentation] ポドプラニン結合阻害能を持つCLEC-2結合低分子化合物リガンド2016

    • Author(s)
      井上克枝,新森英之,長田誠,白井俊光,望月ちひろ,小嶋聡一,斎藤臣雄,佐々木知幸,井上修,尾崎由基男
    • Organizer
      第38回日本血栓止血学会学術集会
    • Place of Presentation
      奈良春日野国際フォーラム(奈良・奈良)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 血小板CLEC-2は肺中皮細胞分化を介して呼吸機能獲得に寄与する2016

    • Author(s)
      築地長治,井上修,田村彰吾,白井俊光,佐々木知幸,佐藤金夫,尾崎由基男,井上克枝
    • Organizer
      第38回日本血栓止血学会学術集会
    • Place of Presentation
      奈良春日野国際フォーラム(奈良・奈良)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] CLEC-2依存性血小板凝集を惹起する蛇毒ロドサイチンの遺伝子組換え体の作製と機能解析2015

    • Author(s)
      佐々木 知幸, 田村 彰吾, 白井 俊光, 築地 長治, 佐藤 金夫, 井上 克枝, 尾崎 由基男
    • Organizer
      BMB2015(第38回日本分子生物学会年会/第88回日本生化学会大会 合同大会)
    • Place of Presentation
      神戸ポートアイランド(兵庫・神戸)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Construction of expression system for biologically functional recombinant rhodocytin.2015

    • Author(s)
      Tomoyuki Sasaki, Shogo Tamura, Toshiaki Shirai, Nagaharu Tsukiji, Kaneo Satoh, Katsue Suzuki-Inoue, Yukio Ozaki
    • Organizer
      ISTH 2015 第25回国際血栓止血学会議
    • Place of Presentation
      トロント(カナダ)
    • Year and Date
      2015-06-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Unexpected role of platelets in lung development depending on a platelet activation receptor, CLEC-2.2015

    • Author(s)
      Nagaharu Tsukiji, Osamu Inoue, Shogo Tamura, Toshiaki Shirai, Tomoyuki Sasaki, Kaneo Satoh, Katsue Suzuki-Inoue, Yukio Ozaki
    • Organizer
      ISTH 2015 第25回国際血栓止血学会議
    • Place of Presentation
      トロント(カナダ)
    • Year and Date
      2015-06-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A novel function of CLEC-2 in megakaryopoiesis: CLEC-2/PDPN microenvironment facilitates expansion and maturation of magakaryocytes.2015

    • Author(s)
      Shogo Tamura, Katsue Suzuki-Inoue, Nagaharu Tsukiji, Toshiaki Shirai, Tomoyuki Sasaki, Makoto Osada, Kaneo Satoh, Yukio Ozaki
    • Organizer
      ISTH 2015 第25回国際血栓止血学会議
    • Place of Presentation
      トロント(カナダ)
    • Year and Date
      2015-06-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血小板活性化受容体CLEC-2結合蛇毒ロドサイチンの機能を保持したリコンビナント体発現系の構築2015

    • Author(s)
      佐々木知幸,田村 彰吾,白井 俊光,築地 長治,佐藤 金夫,井上 克枝,尾崎由基男
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府市総合市民会館(山梨・甲府)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] CLEC-2/PDPN axisによる骨髄内微小環境の可能性:CLEC-2は巨核球造血を促進させる2015

    • Author(s)
      田村 彰吾,井上 克枝,白井 俊光,築地 長治,佐々木知幸,佐藤 金夫,尾崎由基男
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府市総合市民会館(山梨・甲府)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 血小板は肺発生に必須である:血小板CLEC-2の機能解析2015

    • Author(s)
      築地 長治,井上 修,田村 彰吾,白井 俊光,佐々木知幸,佐藤 金夫,井上 克枝,尾崎
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府市総合市民会館(山梨・甲府)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Remarks] 山梨大学医学部臨床検査医学講座

    • URL

      http://www.med.yamanashi.ac.jp/clinical/clin0lab/

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
  • [Patent(Industrial Property Rights)] CLEC-2拮抗剤,血小板凝集抑制剤,抗血栓薬,及び抗転移薬,並びにポルフィリン骨格を有する化合物,及びその製造方法2017

    • Inventor(s)
      井上克枝,佐々木知幸,白井俊光,長田誠,新森英之
    • Industrial Property Rights Holder
      国立大学法人山梨大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-01-04
    • Related Report
      2016 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] CLEC-2拮抗剤,血小板凝集抑制剤,抗血栓薬,及び抗転移薬,並びにポルフィリン骨格を有する化合物,及びその製造方法2016

    • Inventor(s)
      井上克枝,佐々木知幸,白井俊光,長田誠,新森英之
    • Industrial Property Rights Holder
      国立大学法人山梨大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-000267
    • Filing Date
      2016-01-04
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 機能抑制型の遺伝子組換えロドサイチン変異体2016

    • Inventor(s)
      佐々木知幸,白井俊光,井上克枝
    • Industrial Property Rights Holder
      国立大学法人山梨大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-094203
    • Filing Date
      2016-05-09
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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