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Netrin-1 as a novel therapeutic target of medulloblastoma

Research Project

Project/Area Number 18K08984
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionHiroshima International University

Principal Investigator

Nakayama Hironao  広島国際大学, 保健医療学部, 講師 (40512132)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords軸索誘導因子 / 血管新生 / 転移 / 上皮間葉転換 / netrin-1 / 癌幹細胞 / 髄芽腫 / ネトリン
Outline of Final Research Achievements

Netrin-1, a chemoattractant factor in the neuronal system, promotes tumor progression by enhancing angiogenesis and metastasis. Our recent studies demonstrate that netrin-1 promotes medulloblastoma cell invasiveness and angiogenesis in vitro and in vivo. Here, we analyze biological mechanism of netrin-1 in medulloblastoma using mouse model. In a xenograft model, tumor growth was increased when medulloblastoma cells overexpressing netrin-1 were implanted vs. parental cells. Furthermore, immunohistochemical analysis of CD31-expressing endothelial cell demonstrated numerous blood vessels in netrin-1-medulloblastoma. As a molecular mechanism, we find that epithelial mesenchymal transition (EMT)-related molecules are upregulated in netrin-1-medulloblasoma.

Academic Significance and Societal Importance of the Research Achievements

軸索誘導因子(リガンド)およびそのレセプターは、神経軸索伸長の制御因子として同定、解析されてきた。その後の解析によって、軸索誘導因子およびそのレセプターが腫瘍や血管新生にも影響をもたらすことが理解され、腫瘍の治療標的として研究が進んでいる。よって、本研究で明らかになった髄芽腫におけるnetrin-1の分子機序をさらに解析することによって腫瘍・血管新生に対する阻害剤開発に貢献するだけではなく、その他の分野(特に神経変性疾患、炎症関連疾患)への応用も可能であり創薬分野に大きく貢献できるものと考える。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2022 2021 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (9 results)

  • [Journal Article] ゲノム編集技術CRISPR/Cas9を用いたトラスツズマブ耐性乳癌細胞株の作成とその評価2022

    • Author(s)
      松木依理奈,中山寛尚
    • Journal Title

      医療工学雑誌

      Volume: 16 Pages: 13-13

    • NAID

      120007193662

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functionally confirmed compound heterozygous ADAM17 missense loss-of-function variants cause neonatal inflammatory skin and bowel disease 12021

    • Author(s)
      Imoto I, Saito M, Suga K, Kohmoto T, Otsu M, Horiuchi K, Nakayama H, Higashiyama S, Sugimoto M, Sasaki A, Homma Y, Shono M, Nakagawa R, Hayabuchi Y, Tange S, Kagami S, Masuda K
    • Journal Title

      Scientific reports

      Volume: 11 Issue: 1 Pages: 9552-9552

    • DOI

      10.1038/s41598-021-89063-0

    • NAID

      120007188413

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective Effect of Ferulic Acid against Hydrogen Peroxide Induced Apoptosis in PC12 Cells2020

    • Author(s)
      Nakayama Hironao、Nakahara Masako、Matsugi Erina、Soda Midori、Hattori Tomoka、Hara Koki、Usami Ayuki、Kusumoto Chiaki、Higashiyama Shigeki、Kitaichi Kiyoyuki
    • Journal Title

      Molecules

      Volume: 26 Issue: 1 Pages: 90-90

    • DOI

      10.3390/molecules26010090

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anosmin-1 activates vascular endothelial growth factor receptor and its related signaling pathway for olfactory bulb angiogenesis2020

    • Author(s)
      Matsushima Shoko、Shimizu Akio、Kondo Manami、Asano Hirotsugu、Ueno Nobuhiro、Nakayama Hironao、Sato Naoko、Komeno Masahiro、Ogita Hisakazu、Kurokawa-Seo Misuzu
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 188-188

    • DOI

      10.1038/s41598-019-57040-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Semaphorin 3F and Netrin-1: The Novel Function as a Regulator of Tumor Microenvironment2018

    • Author(s)
      Nakayama Hironao、Kusumoto Chiaki、Nakahara Masako、Fujiwara Akira、Higashiyama Shigeki
    • Journal Title

      Frontiers in Physiology

      Volume: 9

    • DOI

      10.3389/fphys.2018.01662

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 経口摂取されたフェルラ酸の生体内挙動に関する研究2021

    • Author(s)
      宇佐美歩樹,原 亘輝,橋本桂樹,服部友香,曽田 翠,中山寛尚,村瀬仁章,北市清幸
    • Organizer
      第12回岐阜薬科大学機能性健康食品研究講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] mTOR阻害剤評価のための分子標的薬耐性乳癌細胞株の作製2021

    • Author(s)
      松木依理奈,中原正子,楠本智章,中山寛尚
    • Organizer
      日本医療検査科学会第53回大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 遺伝子編集技術CRISPR/Cas9を用いたトラスツズマブ耐性乳癌細胞株の作製と解析2021

    • Author(s)
      原翔一,森岡海,松木依理奈,長島大輝,中原正子,楠本智章,中山寛尚
    • Organizer
      第15回日本臨床検査学教育学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] セマフォリン受容体NRP2アイソフォームの機能解析2021

    • Author(s)
      松木依理奈,中原正子,楠本智章,中山寛尚
    • Organizer
      第15回日本臨床検査学教育学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] フェルラ酸による神経細胞保護作用の分子メカニズム解析2020

    • Author(s)
      中原正子,松木依理奈,楠本智章,曽田翠,原亘輝,宇佐美歩樹,服部友香,東山繁樹,北市清幸,中山寛尚
    • Organizer
      第61回日本生化学会中国・四国支部例会
    • Related Report
      2020 Research-status Report
  • [Presentation] PTEN欠損乳癌細胞における軸索誘導因子セマフォリン3Fシグナル解析2020

    • Author(s)
      松木依理奈,中原正子,楠本智章,東山繁樹,中山寛尚
    • Organizer
      第61回日本生化学会中国・四国支部例会
    • Related Report
      2020 Research-status Report
  • [Presentation] Semaphorin 3F inhibits breast tumor angiogenesis and metastasis via Akt-mTOR pathway.2020

    • Author(s)
      Hironao Nakayama, Akari Murakami, Yoshiaki Kamei, Yasutsugu Takada and Shigeki Higashiyama
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] フェルラ酸の生体内挙動と脳機能への影響2020

    • Author(s)
      北市清幸,中山寛尚
    • Organizer
      第11回フェルラ酸研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] Netrin-1シグナルに着目した髄芽腫転移メカニズム解析2019

    • Author(s)
      8.後藤大尚,尾野達郎,中原正子,楠本智章,藤原章,東山繁樹,中山寛尚
    • Organizer
      第14回日本臨床検査学教育学会
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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