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Functional analysis of fibulin-7 in glioma

Research Project

Project/Area Number 17K08770
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionJuntendo University

Principal Investigator

de Vega Susana  順天堂大学, 医学部, 非常勤助教 (30623590)

Co-Investigator(Kenkyū-buntansha) 岡田 保典  順天堂大学, 医学(系)研究科(研究院), 客員教授 (00115221)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords神経膠腫 / 細胞外マトリックス / フィビュリン-7 / 組織内微小環境 / 異常血管形成 / 血管内皮細胞 / 周皮細胞 / 組織内微 / 小環境 / 腫瘍 / 浸潤 / 血管形成 / Fibulin-7
Outline of Final Research Achievements

Malignant transformation and abnormal angiogenesis of glioma may involve a tissue microenvironment created by the production of extracellular matrix (ECM). Here we show that fibulin-7 (Fbln7), an ECM molecule, is overexpressed in endothelial cells and pericytes of abnormal blood vessels in glioblastoma. Vascular endothelial cells stimulated with VEGF upregulate Fbln7, which specifically binds to angiopoietin-1 (Ang1), resulting in suppression of Ang1-Tie2 signaling. In a coculture assay using HUVEC and HBVP, multilayered and irregular-shaped tube-like structures of HUVEC were induced with 500 ng/ml VEGF.VEGF-induced aberrant tube-like structures were attenuated with antibody or synthetic peptides specific to Fbln7 or knockdown of Fbln7. These data demonstrate that Fbln7 is overexpressed by endothelial cells and pericytes of the abnormal microvessels in glioblastoma and suggest that Fbln7 may contribute to the aberrant vessel formation by modulation of the Ang1/Ang2-Tie2 axis.

Academic Significance and Societal Importance of the Research Achievements

膠芽腫は術後の再発や放射線療法や化学療法の治療効果は限定的であることから、きわめて予後不良である。本研究で得られたFbln7によるAng1との特異的な結合とそれによるAng2-Tie2シグナル優位に基づく異常血管新生のデータは、再発性膠芽腫患者に現在汎用されている抗VEGF抗体薬と化学療法の併用療法に、Ang1の正常化を誘導する治療法を加えることの重要性を示唆している。

Report

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

    (17 results)

All 2020 2019 2018 2017

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

  • [Journal Article] Implication of HYBID (Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization) in Hyaluronan Degradation by Synovial Fibroblasts in Patients with Knee Osteoarthritis.2020

    • Author(s)
      Shiozawa J, de Vega S, Cilek MZ, Yoshinaga C, Nakamura T, Kasamatsu S, Yoshida H, Kaneko H, Ishijima M, Kaneko K, Okada Y.
    • Journal Title

      American Journal of Pathology

      Volume: 190 Issue: 5 Pages: 1046-1058

    • DOI

      10.1016/j.ajpath.2020.01.003

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fibulin-7 C-terminal fragment and its active synthetic peptide suppress choroidal and retinal neovascularization2020

    • Author(s)
      Ikeuchi Tomoko、Kanan Yogita、Long Da、de Vega Susana、Hozumi Kentaro、Nomizu Motoyoshi、Campochiaro Peter A.、Yamada Yoshihiko
    • Journal Title

      Microvascular Research

      Volume: 129 Pages: 103986-103986

    • DOI

      10.1016/j.mvr.2020.103986

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The extracellular domain of teneurin-4 promotes cell adhesion for oligodendrocyte differentiation2020

    • Author(s)
      Hayashi Chikako、Suzuki Nobuharu、Mabuchi Yo、Kikura Naomi、Hosoda Yukina、de Vega Susana、Akazawa Chihiro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 523 Issue: 1 Pages: 171-176

    • DOI

      10.1016/j.bbrc.2019.12.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression and Characterization of Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization: HYBID, Alias KIAA1199 and CEMIP.2020

    • Author(s)
      de Vega S, Yoshida H, Okada Y
    • Journal Title

      Methods Mol Biol

      Volume: 2132 Pages: 129-138

    • DOI

      10.1007/978-1-0716-0430-4_1

    • ISBN
      9781071604298, 9781071604304
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Fibulin-7 is overexpressed in glioblastomas and modulates glioblastoma neovascularization through interaction with angiopoietin-12019

    • Author(s)
      Susana de Vega, Akihide Kondo, MarioSuzuki, Hajime Arai, Shabierjiang Jiapaer, Hemragul Sabit, Mitsutoshi Nakada, Tomoko Ikeuchi, Muneaki Ishijima, Eri Arikawa-Hirasawa, Yoshihiko Yamada and Yasunori Okada
    • Journal Title

      International Journal of Cancer

      Volume: xx Issue: 8 Pages: 2157-2169

    • DOI

      10.1002/ijc.32306

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The transcription factor AmeloD stimulates epithelial cell motility essential for tooth morphology.2019

    • Author(s)
      Chiba Y, He B, Yoshizaki K, Rhodes C, Ishijima M, Bleck CKE, Stempinski E, Chu EY, Nakamura T, Iwamoto T, de Vega S, Saito K, Fukumoto S, Yamada Y
    • Journal Title

      J Biol Chem

      Volume: 294(10) Issue: 10 Pages: 3406-3418

    • DOI

      10.1074/jbc.ra118.005298

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Extracellular Protein Fibulin-7 and Its C-Terminal Fragment Have In Vivo Antiangiogenic Activity2018

    • Author(s)
      Ikeuchi Tomoko、de Vega Susana、Forcinito Patricia、Doyle Andrew D.、Amaral Juan、Rodriguez Ignacio R.、Arikawa-Hirasawa Eri、Yamada Yoshihiko
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 17654-17654

    • DOI

      10.1038/s41598-018-36182-w

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification of the Novel Tooth-Specific Transcription Factor AmeloD2018

    • Author(s)
      He B.、Chiba Y.、Li H.、de Vega S.、Tanaka K.、Yoshizaki K.、Ishijima M.、Yuasa K.、Ishikawa M.、Rhodes C.、Sakai K.、Zhang P.、Fukumoto S.、Zhou X.、Yamada Y.
    • Journal Title

      Journal of Dental Research

      Volume: 98 Issue: 2 Pages: 234-241

    • DOI

      10.1177/0022034518808254

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell adhesion protein fibulin-7 and its C-terminal fragment negatively regulate monocyte and macrophage migration and functions in vitro and in vivo.2018

    • Author(s)
      Sarangi PP, Chakraborty P, Dash SP, Ikeuchi T, de Vega S, Ambatipudi K, Wahl L, Yamada Y.
    • Journal Title

      FASEB J

      Volume: In press Issue: 9 Pages: 0000-0000

    • DOI

      10.1096/fj.201700686rrr

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Epiprofin Regulates Enamel Formation and Tooth Morphogenesis by Controlling Epithelial-Mesenchymal Interactions During Tooth Development.2017

    • Author(s)
      Nakamura T, Jimenez-Rojo L, Koyama E, Pacifici M, de Vega S, Iwamoto M, Fukumoto S, Unda F, Yamada Y.
    • Journal Title

      J Bone Miner Res.

      Volume: 32 Issue: 3 Pages: 601-610

    • DOI

      10.1002/jbmr.3024

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Role of the matricellular protein Fibulin-7 in glioblastoma vascularization2019

    • Author(s)
      Susana de Vega, Akihide Kondo, Mario Suzuki, Hajime Arai, Shabierjiang Jiapaer, Hemragul Sabit, Mitsutoshi Nakada, Tomoko Ikeuchi, Muneaki Ishijima, Eri Arikawa-Hirasawa, Yoshihiko Yamada and Yasunori Okada
    • Organizer
      The Matricellular Proteins in Tissue Remodeling and Inflammation Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fibulin-7 modulates glioblastoma neovascularization via regulation of the Ang1/Ang2-Tie2 system2019

    • Author(s)
      Susana de Vega, Mitsutoshi Nakada, and Yasunori Okada
    • Organizer
      第78回 日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Understanding the Challenges in Glioblastoma Treatment2019

    • Author(s)
      Susana de Vega, Yasunori Okada
    • Organizer
      Ⅱ Encuentro de ACE Japon (II Meeting of Spanish Researchers in Japan
    • Related Report
      2019 Annual Research Report
  • [Presentation] Fibulin-7 overproduction contributes to glioma vascularization via interaction with angiopoietin-12018

    • Author(s)
      Susana de Vega, Akihide Kondo, Mario Suzuki, Eri Arikawa-Hirasawa and Yasunori Okada
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Overexpression of Fibulin-7 Modulates the Ang1-Tie2 System and Contributes to the Aberrant Vasculature in Glioblastoma2018

    • Author(s)
      Susana de Vega, Akihide Kondo, Mario Suzuki, Eri Arikawa-Hirasawa, Yasunori Okada
    • Organizer
      Matrix Biology Europe
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Fibulin-7, a non-elastogenic short fibulin, modulates the abnormal vascularization in glioblastoma brain tumo2018

    • Author(s)
      Susana de Vega
    • Organizer
      第2回エラスチン・関連分子研究会学術集会出張報告書
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Analysis of the expression and prospective role of Fibulin-7 in aberrant blood vessel formation in glioblastoma2017

    • Author(s)
      Susana de Vega, Akihide Kondo, Mario Suzuki, Eri Arikawa-Hirasawa and Yasunori Okada
    • Organizer
      第49回日本結合組織学会学術大会抄録
    • Related Report
      2017 Research-status Report

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

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