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Roles of vascular niche in pathophysiology of leukemia and lynphoma

Research Project

Project/Area Number 17K09941
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionJuntendo University

Principal Investigator

Hattori Koichi  順天堂大学, 医学(系)研究科(研究院), 特任先任准教授 (10360116)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords細胞・組織 / 生体分子 / シグナル伝達 / 免疫制御学 / 血管内皮 / アンジオクライン因子 / 血液線維素溶解系
Outline of Final Research Achievements

In this study, we evaluate the roles of vascular niche including tumor endothelial cells for hematological malignancies (leukemia, lymphoma, and related diseases), and during inflammatory disease progression. Here, we could establish a murine model of hematological malignancies and inflammatory diseases and suggest tissue-specific endothelium establishes specialized vascular niches that deploy sets of fibrinolytic factors matrix metalloproteinases, angiogenic and growth factors like epidermal growth factor like-domain 7 (Egfl7), known as angiocrine factors are distributed by organ-specific endothelium. Additionally, we could show these cues participate actively in the induction, specification, patterning, and guidance of tumor and inflammatory diseases progression and severity, as well as in the maintenance of homeostasis and metabolism through the crosstalk between endothelial cells and mesenchymal or hematological lineage cells driven by cytokines and chemokines.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義として、アンジオクライン因子が、白血病・リンパ腫、そしてこれらの関連疾患の病態において果たす役割を明らかにしたこと、そしてこれを通じて、血管内皮を中心とした複数の系統細胞の相互連関-血管ニッチによるホメオスタシス維持機構をアンジオクラインシステムと捉え、多くの生命現象、疾患病態を血管内皮障害の視点から解明したことが挙げられる。さらに、社会的意義の観点から、本研究で得られた知見を基礎として、白血病・リンパ腫などの血液腫瘍性疾患、炎症性疾患に対するアンジオクライン因子を標的とした新しい分子療法の可能性を研究成果として提示できたことは、社会への還元性を有した重要な研究と評価できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (25 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results) Book (1 results)

  • [Journal Article] The EGFL7-ITGB3-KLF2 axis enhances survival of multiple myeloma in preclinical models.2020

    • Author(s)
      Salama Y, Andries H, Yokoyama K, Takahashi S Hattori K and Heissig B,.
    • Journal Title

      Blood Adv

      Volume: in press Issue: 6 Pages: 1021-1037

    • DOI

      10.1182/bloodadvances.2019001002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 腸管外合併症に対するGMAの有効性2020

    • Author(s)
      長田太郎 野村収 服部浩一
    • Journal Title

      日本アフェレーシス学会雑誌

      Volume: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 線溶系と炎症性疾患2020

    • Author(s)
      服部浩一、 高橋聡、 長田太郎、Heissig Beate
    • Journal Title

      日本血栓止血学会雑誌

      Volume: -

    • NAID

      130007887022

    • Related Report
      2019 Annual Research Report
  • [Journal Article] The fibrinolytic factor tPA drives LRP1-mediated melanoma growth and metastasis2019

    • Author(s)
      Salama Y, Lin SY, Dhahri D, Hattori K, Heissig B
    • Journal Title

      FASEB J

      Volume: 33 Issue: 3 Pages: 3465-3480

    • DOI

      10.1096/fj.201801339rrr

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 炎症性腸疾患と線溶系2019

    • Author(s)
      服部浩一
    • Journal Title

      日本血栓止血学会雑誌

      Volume: 28 Pages: 618-622

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacological targeting of plasmin prevents lethality and tissue damage in a murine model of macrophage activation syndrome2017

    • Author(s)
      1.Shimazu H, Munakata S, Tashiro Y, Salama Y, Eiamboonser S, Ohta Y, Onoda H, Tsuda Y, Okada Y, Nakauchi H, Heissig B and Hattori K
    • Journal Title

      Blood

      Volume: 印刷中 Issue: 1 Pages: 59-72

    • DOI

      10.1182/blood-2016-09-738096

    • Related Report
      2019 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The role of plasmin in the pathogenesis of murine multiple myeloma2017

    • Author(s)
      Eiamboonsert S, Salama Y, Watarai H, Dhahri D, Tsuda Y, Okada Y, Hattori K, Heissig B.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 488 Issue: 2 Pages: 387-392

    • DOI

      10.1016/j.bbrc.2017.05.062

    • Related Report
      2019 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice.2017

    • Author(s)
      Honjo K, Munakata S, Tashiro Y, Salama Y, Shimazu H, Eiamboonsert S, Dhahri D, Ichimura A, Dan T, Miyata T, Takeda K, Sakamoto K, Hattori K, Heissig B.
    • Journal Title

      FASEB Journal

      Volume: - Issue: 6 Pages: 2625-2637

    • DOI

      10.1096/fj.201600871rr

    • Related Report
      2019 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The angiogenic factor Egfl7 alters thymogenesis by activating Flt3 signaling2017

    • Author(s)
      Salama Yousef、Hattori Koichi、Heissig Beate
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 490 Issue: 2 Pages: 209-216

    • DOI

      10.1016/j.bbrc.2017.06.023

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Platelet functions in development and regeneration2017

    • Author(s)
      服部浩一
    • Journal Title

      Japanese Journal of Thrombosis and Hemostasis

      Volume: 28 Issue: 5 Pages: 589-596

    • DOI

      10.2491/jjsth.28.589

    • NAID

      130006831909

    • ISSN
      0915-7441, 1880-8808
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 臓器特異的血管内皮によるアンジオクラインシステム制御機構の解明2020

    • Author(s)
      服部浩一, 高橋聡, Heissig Beate
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HSC expansion and mobilization from bone marrow niche2019

    • Author(s)
      Hattori K
    • Organizer
      JOINT WORK SHOP NORWAY AND JAPAN IN REGENERATIVE MEDICINE
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Roles of the fibrinolytic system in the pathogenesis of inflammatory diseases2019

    • Author(s)
      Hattori K, Takahashi S, Heissig B
    • Organizer
      第41回日本血栓止血学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] アンジオクラインシステムによる組織修復とリモデリング制御機構2019

    • Author(s)
      服部浩一, 高橋聡, Heissig Beate
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
  • [Presentation] Angiocrine system regulates macrophage -dependent aberrant tissue repair and remodeling2019

    • Author(s)
      Hattori K, Takahashi S, Heissig B
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アンジオクラインシステムによるGVHD病態制御機構の解明2019

    • Author(s)
      服部浩一、Heissig Beate、高橋聡
    • Organizer
      第10回日本血液疾患免疫療法学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Functional analysis of the fibrinolytic system in the pathogenesis of hemophagocytic syndrome2019

    • Author(s)
      Shimazu H. Tashiro Y. Nakauchi H. Heissig B, HattoriK
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HSC expansion and mobilization from bone marrow niche2018

    • Author(s)
      Koichi Hattori
    • Organizer
      JOINT WORK SHOP NORWAY AND JAPAN IN REGENERATIVE MEDICINE
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Angiocrine system regulates macrophage -dependent aberrant tissue repair and remodeling2018

    • Author(s)
      Hattori K, Takahashi S and Heissig B
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] アンジオクラインシステムによるGVHD病態制御機構の解明2018

    • Author(s)
      服部浩一、Heissig Beate、高橋聡
    • Organizer
      第10回日本血液疾患免疫療法学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] アンジオクライン因子による間葉系幹細胞動態2018

    • Author(s)
      服部浩一、高橋聡、Heissig Beate.
    • Organizer
      第17回日本再生医療学会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Functional analysis of the fibrinolytic system in the pathogenesis of hemophagocytic syndrome.2017

    • Author(s)
      Shimazu H. Tashiro Y. Nakauchi H. Heissig B, HattoriK.
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Angiocrine factors expand mesenchymal stromal cells n bone marrow niche.2017

    • Author(s)
      Hattori K, Takahashi S and Heissig B.
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pharmacological targeting of plasmin prevents lethality and tissue damage in a murine model of macrophage activation syndrome.2017

    • Author(s)
      Shimazu H, Munakata S, Tashiro Y, Salama Y, Eiamboonser S, Ohta Y, Onoda H, Tsuda Y, Okada Y, Nakauchi H, Heissig B and Hattori K.
    • Organizer
      第13回麒麟塾,
    • Related Report
      2017 Research-status Report
  • [Book] 動物/疾患モデルの 作製技術・病態解析・評価手法2017

    • Author(s)
      多田昇弘、田中光一、大塚正人、平原 潔、服部浩一(全著者数87名、59番目)
    • Total Pages
      428
    • Publisher
      技術情報協会
    • ISBN
      9784861046650
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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