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Role of proteoglycans in diseases: Regulation of cell behavior and maintenance of tissue structure

Research Project

Project/Area Number 25293096
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionAichi Medical University

Principal Investigator

WATANABE Hideto  愛知医科大学, 付置研究所, 教授 (90240514)

Co-Investigator(Renkei-kenkyūsha) SUGIURA Nobuo  愛知医科大学, 分子医科学研究所, 准教授 (90454420)
NAGAI Naoko  愛知医科大学, 分子医科学研究所, 助教 (00367799)
TSUCHIMOTO Jun  愛知医科大学, 分子医科学研究所, 助教 (70632868)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2013: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsプロテオグリカン / バーシカン / 遺伝子改変マウス / 創傷治癒 / がん微小環境 / 腫瘍 / 細胞外マトリックス / 細胞外微小環境 / 腫瘍微小環境 / 間質 / 腫瘍増殖
Outline of Final Research Achievements

Versican (Vcan) is a large chondroitin sulfate proteoglycan in the extracellular matrix (ECM). Here, we report that Vcan inhibits tumor growth. Local depletion of stromal Vcan expression in Vcan<flox/flox> mice by infecting cre-expressing adenoviruses facilitates growth of QRsP11 fibrosarcoma cells, which is observed as early as day 7, followed by tumor angiogenesis as early as day 14. Loss of local Vcan decreases tumor stroma including fibroblasts and dense collagen fibers, and alters localization of TGFbeta;. These results demonstrate that stromal Vcan inhibits tumor growth by maintaining the ECM structure and TGFbeta-signaling. We also analyzed Vcan<delta3/delta3> embryos, whose Vcan lacks the A subdomain of the G1 domain and exhibits less hyaluronan-binding activity, and found that Vcan plays an important role in formation of dermis. These results clearly demonstrate that Vcan contributes to ECM formation.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (25 results)

All 2017 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Acknowledgement Compliant: 4 results,  Open Access: 5 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 7 results) Remarks (4 results)

  • [Int'l Joint Research] Center for Medical Paracytology/Dept of Immunology and Microbiology/University of Copenhagen(Denmark)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Versican A-subdomain is required for its adequate function in dermal development.2017

    • Author(s)
      Hatano S, Nagai N, Sugiura N, Tsuchimoto J, Isogai z, Kimata K, Ota A, Karnan S, Hosokawa Y, Watanabe H
    • Journal Title

      Connect Tissue Res

      Volume: 印刷中 Issue: 2 Pages: 178-190

    • DOI

      10.1080/03008207.2017.1324432

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Molecular dissection of placental malaria protein VAR2CSA interaction with a chemo-enzymatically synthesized chondroitin sulfate library.2016

    • Author(s)
      Sugiura N, Clausen TM, Shioiri T, Gustavsson T, Watanabe H, Salanti A.
    • Journal Title

      Glycoconj J

      Volume: 33 Pages: 985-994

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sequence determination of synthesized chondroitin sulfate dodecasaccharides.2016

    • Author(s)
      Shioiri T, Tsuchimoto J, Watanabe H, Sugiura N
    • Journal Title

      Glycobiology

      Volume: 22 Issue: 6 Pages: 596-602

    • DOI

      10.1093/glycob/cww008

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Assessment of pulp regeneration induced by stem cell therapy by magnetic resonance imaging.2016

    • Author(s)
      Iohara K, Fujita M, Ariji Y, Yoshikawa M, Watanabe H, Takashima A, Nakashima M
    • Journal Title

      J Endod

      Volume: 42 Issue: 3 Pages: 397-401

    • DOI

      10.1016/j.joen.2015.11.021

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Host stromal versican is essential for cancer-associated fibroblast function to inhibit cancer growth.2016

    • Author(s)
      Fanhchaksai K, Okada F, Nagai N, Pothacharoen P, Kongtawelert P, Hatano S, Makino S, Nakamura T, Watanabe H
    • Journal Title

      Int J Cancer

      Volume: 138 Pages: 630-641

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Callicarpa longissima extract, carnosol-rich, potently inhibits melanogenesis in B16F10 melanoma cells2016

    • Author(s)
      M. Yamahara, K. Sugimura, A. Kumagai, H. Fuchino, A. Kuroi, M. Kagawa, Y. Itoh, H. Kawahara, Y. Nagaoka, O. Iida, N. Kawahara, H. Takemori, H. Watanabe
    • Journal Title

      J. Nat. Med.

      Volume: 70 Issue: 1 Pages: 28-35

    • DOI

      10.1007/s11418-015-0933-5

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Sulfation of the bikunin chondroitin sulfate chain determines heavy chain·hyaluronan complex formation2013

    • Author(s)
      Lord MS, Day AJ, Youssef P, Zhuo L, Watanabe H, Caterson B, Whitelock JM.
    • Journal Title

      J Biol Chem.

      Volume: 288 Issue: 32 Pages: 22930-22941

    • DOI

      10.1074/jbc.m112.404186

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of heparan sulfate 6-O-sulfation in regulation of energy metabolism and alteration of thyroid hormone levels in male mice.2013

    • Author(s)
      Nagai N, Habuchi H, Sugaya N, Nakamura M, Imamura T, Watanabe H, Kimata K.
    • Journal Title

      Glycobiology

      Volume: 23 Issue: 8 Pages: 980-992

    • DOI

      10.1093/glycob/cwt037

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chondroitinase from baculovirus Bombyx mori nucleopolyhedrovirus and chondroitin sulfate from silkworm Bombyx mori.2013

    • Author(s)
      Sugiura, N., Ikeda, M., Shioiri, T., Yoshimura, M., Kobayashi, M. and Watanabe, H.
    • Journal Title

      Glycobiology

      Volume: 23 Issue: 12 Pages: 1520-1530

    • DOI

      10.1093/glycob/cwt082

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] The extracellular matrix: effects on ageing and disease2016

    • Author(s)
      Hideto Watanabe
    • Organizer
      2nd HARC Conference
    • Place of Presentation
      ポーランド、ウッチ
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of versican, and chondrotin sulfate in development and diseases2015

    • Author(s)
      Hideto Watanabe
    • Organizer
      5th FEBS Advanced Lecture Course FEBS &#8211; MPST 2015
    • Place of Presentation
      Rhodes Island, Greece
    • Year and Date
      2015-09-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 真皮細胞外マトリックス:構築と病態による変容2015

    • Author(s)
      渡辺秀人
    • Organizer
      第41回日本熱傷学会総会・学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-06-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 細胞外マトリックスプロテオグリカンによる腫瘍微小環境の形成と腫瘍制御2015

    • Author(s)
      ファンチャクサイ・カンダ,岡田 太,永井尚子、コンタウェラート・プラチャ、幡野その子、渡辺秀人
    • Organizer
      第47回日本結合組織学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 宿主発現バーシカンによる腫瘍増殖制御2014

    • Author(s)
      渡辺秀人,ファンチャクサイカンダ,岡田 太,コンタウェラートプラチャ
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 成長後の循環器に対するバーシカンの役割2014

    • Author(s)
      幡野その子、牧野伸司、ミッタル ニシャント、中邨智之、木全弘治、渡辺秀人
    • Organizer
      第46回日本結合組織学会第51回マトリックス研究会合同学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-06-05 – 2014-06-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Host versican provides microenvironment that inhibits tumor growth2014

    • Author(s)
      Kanda Fanhchaksai, Futoshi Okada, Sonoko Hatano, Prachya Kongtawelert, Hideto Watanabe
    • Organizer
      第46回日本結合組織学会第51回マトリックス研究会合同学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-06-05 – 2014-06-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of chondroitin sulfate proteoglycans in development and disease2014

    • Author(s)
      Hideto Watanabe
    • Organizer
      2014 KSBMB Annual Meeting
    • Place of Presentation
      ソウル
    • Year and Date
      2014-05-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Role of large chondroitin sulfate proteoglycans in development and disease2014

    • Author(s)
      Hideto Watanabe
    • Organizer
      8th Annual Symposium in Institute of Human-Environment Interface Biology
    • Place of Presentation
      ソウル
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Roles of versican in cardiovascular development2013

    • Author(s)
      Sonoko hatano, Shinji Makino, Koji Kimata, Hideto Watanabe
    • Organizer
      International conference on hyaluronan (HA2013)
    • Place of Presentation
      オクラホマ
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Role of versican in heart and skeletal development2013

    • Author(s)
      Hideto Watanabe
    • Organizer
      9th Pan Pacific Connective Tissue Societies Symposium
    • Place of Presentation
      香港
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Remarks] 愛知医科大学分子医科学研究所

    • URL

      http://www.aichi-med-u.ac.jp/su10/su1009/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 愛知医科大学戦略的研究基盤形成支援事業

    • URL

      http://amu-strategy.org/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 分子医科学研究所 愛知医科大学

    • URL

      http://www.aichi-med-u.ac.jp/su10/su1009/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 愛知医科大学 戦略的研究基盤形成支援事業

    • URL

      http://amu-strategy.org/

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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