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Mechanisms of thrombus formation common to cancer and infectious diseases

Research Project

Project/Area Number 22K19610
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 57:Oral science and related fields
Research InstitutionHokkaido University

Principal Investigator

HIDA Kyoko  北海道大学, 歯学研究院, 教授 (40399952)

Co-Investigator(Kenkyū-buntansha) 澤 洋文  北海道大学, 人獣共通感染症国際共同研究所, 兼務教員 (30292006)
Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords血管内皮細胞 / 新型コロナ感染症 / 腫瘍 / 血栓症 / 好中球 / 血栓 / 感染症
Outline of Research at the Start

SARS-CoV-2感染若齢・高齢マウスを用いて,各モデルについて感染初期と後期の2点で肺のサンプリングを行う.血管内皮細胞を単離・濃縮し,scRNAseq解析を実施する.重症化モデルと非重症化モデルの比較解析により,重症化モデルに特徴的なクラスターを同定する.さらに感染初期と後期でTrajectory解析によりクラスターの遷移状態を推定し血栓症の発症メカニズムを探る.また,肺胞上皮細胞や免疫細胞など血管内皮細胞以外の間質細胞との相互作用は,肺全体の公開scRNAseqデータとの統合解析を実施して血管内皮-間質細胞相互作用のダイナミクス,血管内皮による血栓形成促進分子機構を明らかにする.

Outline of Final Research Achievements

Lungs of aged and young mice were sampled, vascular endothelial cells were isolated and enriched, and RNAseq was performed. We analysed the pathogenesis of thrombosis without characteristic of the severe disease model. For tumor endothelial cells, we isolated endothelial cells and non-endothelial cell fractions from tumors of different grades and from anti-cancer-treated mouse models using our previously established method and identified factors involved in thrombogenesis, including known factors such as vWF, P-selectin and thrombomodulin. In addition to known factors such as vWF, P-selectin and thrombomodulin, novel molecules involved in blood coagulation and immune cell migration were identified. The effects of the molecular inhibitor candidates on thrombogenesis and vasculitis were analysed histopathologically in animal models.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により,血管内皮細胞が免疫細胞や血小板,あるいは赤血球に対する作用が明らかになった.感染症と癌における共通した血栓症発症の分子機序を明らかにした.癌患者の予後が改善する中,心血管イベント発生予防は喫緊の課題でありアンメットメディカルニーズのひとつである.新型コロナ感染症重症化に対する血栓症診断,治療法はまだ確立されておらず,本研究成果により新たな治療戦略開発ににつながるものと考えられる.

Report

(2 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (19 results)

All 2024 2023

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (14 results) (of which Int'l Joint Research: 5 results,  Invited: 12 results)

  • [Journal Article] Oral bacterium Streptococcus mutans promotes tumor metastasis via thrombosis formation2024

    • Author(s)
      Yu L, Hong Y, Maishi N, Yanagawa Matsuda A, Hida Y, Hasebe A,Kitagawa Y, Hida K
    • Journal Title

      Cancer Science

      Volume: 115(2) Issue: 2 Pages: 648-659

    • DOI

      10.1111/cas.16010

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Viral uptake and pathophysiology of the lung endothelial cells in age‐associated severe SARS‐CoV‐2 infection models2023

    • Author(s)
      Tsumita Takuya、Iimura Tadahiro、Sawa Hirofumi、Hida Kyoko et al.
    • Journal Title

      Aging Cell

      Volume: 23 Issue: 2

    • DOI

      10.1111/acel.14050

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low-dose metronomic cisplatin as an antiangiogenic and anti-inflammatory strategy for cancer2023

    • Author(s)
      Kikuchi Hiroshi、Maishi Nako、Yu Li、Jia Zi、Li Cong、Sato Masumi、Takeda Ryo、Ishizuka Keita、Hida Yasuhiro、Shinohara Nobuo、Hida Kyoko
    • Journal Title

      British Journal of Cancer

      Volume: 130 Issue: 2 Pages: 336-345

    • DOI

      10.1038/s41416-023-02498-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] miR-1246 in tumor extracellular vesicles promotes metastasis via increased tumor cell adhesion and endothelial cell barrier destruction2023

    • Author(s)
      Morimoto Masahiro、Maishi Nako、Tsumita Takuya、Alam Mohammad Towfik、Kikuchi Hiroshi、Hida Yasuhiro、Yoshioka Yusuke、Ochiya Takahiro、Annan Dorcas A.、Takeda Ryo、Kitagawa Yoshimasa、Hida Kyoko
    • Journal Title

      Frontiers in Oncology

      Volume: 13 Pages: 973871-973871

    • DOI

      10.3389/fonc.2023.973871

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angiogenic inhibitor pre-administration improves the therapeutic effects of immunotherapy2023

    • Author(s)
      Sato M, Maishi N, Hida Y, Yanagawa-Matsuda A, Alam MT, Sakakibara-Konishi J, Nam JM, Onodera Y, Konno S, Hida K
    • Journal Title

      Cancer Medicine

      Volume: 12(8) Issue: 8 Pages: 9760-9773

    • DOI

      10.1002/cam4.5696

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Presentation] 腫瘍血管内皮細胞と炎症老化2024

    • Author(s)
      樋田京子
    • Organizer
      第113回日本病理学会総会, 先端的分子病理学講習会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Contribution of tumor endothelial cells in tumor progression2024

    • Author(s)
      Hida K
    • Organizer
      The 1st International Symposium on Cancer Immunology and Immunotherapy
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 血管病態研究からがん臨床への展開の試み2024

    • Author(s)
      樋田京子
    • Organizer
      第42回日本口腔腫瘍学会総会・学術大会特設講演
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 血管―微小環境ネットワークとがんの進展2023

    • Author(s)
      樋田京子
    • Organizer
      第68回日本口腔外科学会総会・学術大会シンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 腫瘍血管内皮細胞による血栓形成促進2023

    • Author(s)
      樋田京子
    • Organizer
      第64回日本脈管学会学術総会シンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Vascular Biology 20232023

    • Author(s)
      Yu L, Nako Maishi N, Akahori E, Hong Y, Hasebe A, Takeda R, Matsuda A, Hida Y, Kitagawa Y, Hida K
    • Organizer
      The oral bacterium Streptococcus mutans promotes tumor metastasis by inducing vascular inflammation and thrombosis
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腫瘍血管内皮細胞とがん微小環境2023

    • Author(s)
      樋田京子
    • Organizer
      第88回日本泌尿器科学会 東部総会 札幌 特別講演
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 腫瘍血管内被細胞によるがん転移促進2023

    • Author(s)
      樋田京子
    • Organizer
      第65回歯科基礎医学会学術大会アップデートシンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 血管の多様性とがんの悪性化2023

    • Author(s)
      樋田京子
    • Organizer
      第41回日本ヒト細胞学会学術集会シンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] がん, 感染症における血管―微小環境ネットワーク2023

    • Author(s)
      樋田京子
    • Organizer
      第41回日本骨代謝学会学術集会シンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 癌微小環境と血管内皮細胞のネットワーク2023

    • Author(s)
      樋田京子
    • Organizer
      第43回日本骨形態計測学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Vasclar endothelial cell heterogeneity in diseases2023

    • Author(s)
      Hida K
    • Organizer
      The 2023 Conference of Asia Pacific Societies for Extracellular Vesicles(APSEV)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Analysis of lung endotheliopathy in lethal mice infected with mouse- adapted SARS-CoV-22023

    • Author(s)
      Hida K
    • Organizer
      2023 KVBM Annual Meeting & AAVBM in partnership with ICoLA, Seoul
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of lung endotheliopathy in lethal mice infected with mouse- adapted SARS-CoV-22023

    • Author(s)
      Hida K
    • Organizer
      2023 KVBM Annual Meeting & AAVBM in partnership with ICoLA
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research

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Published: 2022-07-05   Modified: 2025-01-30  

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