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The roles of laminin alpha5 in tumor invasion

Research Project

Project/Area Number 26430123
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

KIKKAWA YAMATO  東京薬科大学, 薬学部, 准教授 (20274227)

Co-Investigator(Renkei-kenkyūsha) NOMIZU Motoyoshi  東京薬科大学, 薬学部, 教授 (00311522)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsラミニン / 基底膜 / 細胞外マトリックス / 癌 / 細胞接着 / 細胞運動 / ルテラン / インテグリン
Outline of Final Research Achievements

Epithelial cells stably anchor to basement membrane, whereas malignant tumors pass through it to achieve metastasis. Of basement membrane components, laminin-511 (alpha5, beta1, gamma1; LM-511) is a major isoform in many adult tissues. Several studies have shown that LM-511 promotes not only cell adhesion but also tumor cell migration. Thus, LM-511 can be viewed like two distinct molecules in normal vs. tumor cells. In this study, we focused on 1) the assembly of basement membrane containing LM-511 in tumor microenviroments and 2) the migration of tumor cells adhering to LM-511. The amino acid sequences active for endothelial cell tube formation were identified using synthetic peptides-derived from laminin alpha5 N-terminus. Our results also showed that endogenous LM-511 promotes the formation of cyst structure accompanying with basement membrane. Moreover, we found that the inside-out signal is involved in the transition from static to migratory cell behaviors on LM-511.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (35 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 11 results,  Acknowledgement Compliant: 3 results) Presentation (15 results) (of which Int'l Joint Research: 4 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Washington University in St.Louis(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] National Cancer Centre(シンガポール)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Identification of laminin α5 short arm peptides active for endothelial cell attachment and tube formation.2017

    • Author(s)
      Kikkawa, Y., Sugawara, Y., Harashima, N., Fujii, S., Ikari, K., Kumai, J., Katagiri, F., Hozumi, K., and Nomizu, M.
    • Journal Title

      Journal of Peptide Science

      Volume: 印刷中 Issue: 7-8 Pages: 666-673

    • DOI

      10.1002/psc.2987

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An anti-human lutheran glycoprotein phage antibody inhibits cell migration on laminin-511: epitope mapping of the antibody.2017

    • Author(s)
      Enomoto-Okawa Y, Maeda Y, Harashima N, Sugawara Y, Katagiri F, Hozumi K, Hui KM, Nomizu M, Ito Y, Kikkawa Y
    • Journal Title

      PLoS One

      Volume: 12 Issue: 1 Pages: e0167860-e0167860

    • DOI

      10.1371/journal.pone.0167860

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Biological activity of peptide-conjugated polyion complex matrices consisting of alginate and chitosan.2017

    • Author(s)
      Fujimori, C‡., Kumai, J‡., Nakamura, K., Gu, Y., Hozumi, K., Katagiri, F., Kikkawa, Y., and Nomizu, M
    • Journal Title

      Biopolymers

      Volume: 108 Issue: 1 Pages: 356-366

    • DOI

      10.1002/bip.22983

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Down-regulation of cell adhesion via rho-associated protein kinase (ROCK) pathway promotes tumor cell migration on laminin-5112016

    • Author(s)
      Kikkawa Y, Harashima N, Ikari K, Fujii S, Katagiri F, Hozumi K, Nomizu M
    • Journal Title

      Exp Cell Res

      Volume: 344 Issue: 1 Pages: 76-85

    • DOI

      10.1016/j.yexcr.2016.04.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel hybrid compound of a plinabulin prodrug with an IgG binding peptide for generating a tumor selective noncovalent-type antibody-drug conjugate2016

    • Author(s)
      Muguruma K, Yakushiji F, Kawamata R, Akiyama D, Arima R, Shirasaka T, Kikkawa Y, Taguchi A, Takayama K, Fukuhara T, Watabe T, Ito Y, Hayashi Y
    • Journal Title

      Bioconjug Chem

      Volume: 27 Issue: 7 Pages: 1606-1613

    • DOI

      10.1021/acs.bioconjchem.6b00149

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of spacer length and type on the biological activity of peptide-polysaccharide matrices.2016

    • Author(s)
      Kumai, J, Hozumi, K, Yamada, Y, Katagiri, F, Kikkawa, Y, Nomizu, M
    • Journal Title

      Biopolymers

      Volume: 印刷中 Issue: 4 Pages: 512-520

    • DOI

      10.1002/bip.22785

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural study of cell attachment peptide derived from laminin by molecular dynamics simulation.2016

    • Author(s)
      Yamada, H, Mori, S, Miyakawa, T, Morikawa, R, Katagiri, F, Hozumi, K, Kikkawa, Y, Nomizu, M, Takasu, M
    • Journal Title

      PLoS One

      Volume: 11 Issue: 2 Pages: e0149474-e0149474

    • DOI

      10.1371/journal.pone.0149474

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An efficacy of intensive vitamin D delivery to neointimal hyperplasia in recurrent vascular access stenosis.2016

    • Author(s)
      Sato, T, Iwasaki, Y, Kikkawa, Y, Fukagawa, M
    • Journal Title

      J Vasc Access

      Volume: 17 Issue: 1 Pages: 72-77

    • DOI

      10.5301/jva.5000469

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of cell adhesion through specific integrin crosstalk on mixed peptide-polysaccharide matrices2015

    • Author(s)
      Kentaro Hozumi, Chikara Fujimori, Fumihiko Katagiri, Yamato Kikkawa, Motoyoshi Nomizu
    • Journal Title

      Biomaterials

      Volume: 37 Pages: 73-81

    • DOI

      10.1016/j.biomaterials.2014.10.005

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] がん細胞の接着および運動における基底膜分子ラミニン-511とその受容体Lu/B-CAMの役割2015

    • Author(s)
      吉川大和
    • Journal Title

      生化学

      Volume: 87 Pages: 609-611

    • NAID

      40020650196

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biological activities of the homologous loop regions in the laminin alpha chain LG modules. Biochemistry.2014

    • Author(s)
      Katagiri, F., Hara, T., Yamada, Y., Urushibata, S., Hozumi, K., Kikkawa, Y., Nomizu, M.
    • Journal Title

      Biochemistry

      Volume: 53 Issue: 22 Pages: 3699-3708

    • DOI

      10.1021/bi5003822

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Screening of integrin-binding peptides in a laminin peptide library derived from the mouse laminin β chain short arm regions2014

    • Author(s)
      Katagiri F, Takagi M, Nakamura M, Tanaka Y, Hozumi K, Kikkawa Y, Nomizu M
    • Journal Title

      Arch Biochem Biophys

      Volume: 550-551 Pages: 33-41

    • DOI

      10.1016/j.abb.2014.04.008

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Soluble lutheran/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patients and modulates cellular interaction with laminin-511 in vitro2014

    • Author(s)
      Kikkawa Y, Miwa T, Tanimizu N, Kadoya Y, Ogawa T, Katagiri F, Hozumi K, Nomizu M, Mizuguchi T, Hirata K, Mitaka T
    • Journal Title

      Experimental Cell Research

      Volume: 328 Issue: 1 Pages: 197-206

    • DOI

      10.1016/j.yexcr.2014.07.012

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Identification of laminin alpha5 short arm peptides active for endothelial cell attachment and tube formation.2016

    • Author(s)
      Sugawara Y, Harashima N, Fujii S, Ikari K, Katagiri F, Hozumi K, Nomizu M, Kikkawa Y
    • Organizer
      2016 Annual Meeting the American Society for Cell Biology
    • Place of Presentation
      San Francisco (USA)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The involvement of Lu/B-CAM spectrin binding motif in cell migration on LM-511.2016

    • Author(s)
      Harashima N, Sugawara Y, Ikari K, Katagiri F, Hozumi K, Nomizu M, Kikkawa Y
    • Organizer
      2016 Annual Meeting the American Society for Cell Biology
    • Place of Presentation
      San Francisco (USA)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Down-regulation of cell adhesion via rho-associated protein kinase (ROCK) pathway promotes tumor cell migration on laminin-511.2016

    • Author(s)
      Kikkawa Y, Harashima N, Ikari K, Fujii S, Katagiri F, Hozumi K, Nomizu M
    • Organizer
      American Society for Matrix Biology Biennial Meeting
    • Place of Presentation
      St. Petersburg (USA)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 基底膜の機能解明からバイオマテリアルの創製へ2016

    • Author(s)
      吉川大和、保住建太郎、片桐文彦、野水基義
    • Organizer
      第48回日本結合組織学会学術大会
    • Place of Presentation
      長崎大学、長崎市
    • Year and Date
      2016-06-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] ROCK経路を介したラミニン-511に対する細胞接着の抑制と細胞運動の促進2016

    • Author(s)
      原島望、碇 和樹、藤井翔悟、片桐文彦、保住建太郎、野水基義、吉川大和
    • Organizer
      第48回日本結合組織学会学術大会
    • Place of Presentation
      長崎大学、長崎市
    • Year and Date
      2016-06-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 細胞-基質間における基底膜分子ラミニン-511とその受容体ルテランの役割2016

    • Author(s)
      吉川大和
    • Organizer
      第68回日本細胞生物学会大会
    • Place of Presentation
      京都テルサ、京都市
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Identification of active sequences in N-terminal region of laminin α5 involving endothelial cell attachment.2015

    • Author(s)
      Fujii, S., Harashima,N., Ikari, K., Katagiri, F., Hozumi, K., Nomizu, M., Kikkawa, Y
    • Organizer
      2015 Annual Meeting the American Society for Cell Biology
    • Place of Presentation
      San Diego Convention Center, San Diego (USA)
    • Year and Date
      2015-12-12
    • Related Report
      2015 Research-status Report
  • [Presentation] ラミニン-511上における癌細胞の運動促進メカニズム2015

    • Author(s)
      原島望、藤井翔悟、碇和樹、片桐文彦、保住建太郎、野水基義、吉川大和
    • Organizer
      第三回MatriCellフォーラム
    • Place of Presentation
      三重大学、津
    • Year and Date
      2015-09-12
    • Related Report
      2015 Research-status Report
  • [Presentation] Tumor cell migration on laminin-511 is promoted through the receptor binding reduced with PMA.2015

    • Author(s)
      Kikkawa, Y., Harashima,N., Ikari, K., Fujii, S., Katagiri, F., Hozumi, K., Nomizu, M
    • Organizer
      9th International Conference on Proteoglycans and 10th Pan-Pacific Connective Tissue Societies Symposium
    • Place of Presentation
      Ewha Womans University, Seoul, Korea
    • Year and Date
      2015-08-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ラミニン-511に対する細胞接着の抑制と細胞運動の促進2015

    • Author(s)
      藤井翔吾、碇和樹、片桐文彦、保住建太郎、野水基義、吉川大和
    • Organizer
      第47回日本結合組織学会学術大会
    • Place of Presentation
      コクヨホール、東京
    • Year and Date
      2015-05-15
    • Related Report
      2015 Research-status Report
  • [Presentation] An anti-human Lutheran phage antibody isolated from hepatocellular carcinoma phage library inhibits cell migration on laminin-511.2014

    • Author(s)
      Kikkawa, Y., Enomoto, Y., Ikari, K., Katagiri, F., Hozumi, K., Nomizu, M., and Ito, Y.
    • Organizer
      The 2014 ascb/ifcb meeting
    • Place of Presentation
      Pennsylvania Convention Center, Philadelphia (USA)
    • Year and Date
      2014-12-06 – 2014-12-10
    • Related Report
      2014 Research-status Report
  • [Presentation] Phorbol ester alters cell migration of lung adenocarcinoma on laminin-511.2014

    • Author(s)
      Ikari, K., Fujii, S., Katagiri, F., Hozumi, K., Nomizu, M., and Kikkawa, Y.
    • Organizer
      The 2014 ascb/ifcb meeting
    • Place of Presentation
      Pennsylvania Convention Center, Philadelphia (USA)
    • Year and Date
      2014-12-06 – 2014-12-10
    • Related Report
      2014 Research-status Report
  • [Presentation] Soluble Lutheran glycoprotein/basal cell adhesion molecule is detectable in plasma of hepatocellular carcinoma patiets and modulates cellular interaction with laminin-511 in vitro.2014

    • Author(s)
      Kikkawa, Y., Miwa, T., Tanimizu, N., Kadoya, Y., Ogawa, T., Katagiri, F., Hozumi, K., Nomizu, M., Mizuguchi, T., Hirata, K., and Mitaka, T.
    • Organizer
      American Society for Matrix Biology Biennial Meeting 2014
    • Place of Presentation
      Marriott Key center, Cleveland (USA)
    • Year and Date
      2014-10-12 – 2014-10-15
    • Related Report
      2014 Research-status Report
  • [Presentation] 肝細胞癌由来scFvファージ抗体ライブラリを用いたルテラン特異的抗体の単離2014

    • Author(s)
      吉川 大和、榎元 友里恵、小川 貴穂、片桐 文彦、保住 建太郎、Hui Kam Man、野水 基義、伊東 祐二
    • Organizer
      第21回肝細胞研究会
    • Place of Presentation
      東京医科歯科大学、東京
    • Year and Date
      2014-06-27 – 2014-06-28
    • Related Report
      2014 Research-status Report
  • [Presentation] ラミニンα5鎖受容体ルテラン(Lu/B-CAM)に対するファージ抗体の作製とその評価2014

    • Author(s)
      吉川 大和、榎本 友里恵、小川 貴穂、片桐 文彦、保住 建太郎、Hui Kam Man、野水 基義、伊東 祐二
    • Organizer
      第46回日本結合組織学会学術大会 第61回マトリックス研究会大会 合同学術集会
    • Place of Presentation
      ウインク愛知、名古屋市
    • Year and Date
      2014-06-05 – 2014-06-07
    • Related Report
      2014 Research-status Report
  • [Book] Encyclopedia of Signaling Molecules, 2nd Edition2017

    • Author(s)
      Kikkawa Y, Nishimune H
    • Total Pages
      11
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Remarks] 東京薬科大学 薬学部 病態生化学

    • URL

      http://www.ps.toyaku.ac.jp/wp/byotaiseika/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 吉川大和

    • URL

      http://researchmap.jp/yamatokikkawa/

    • Related Report
      2016 Annual Research Report 2015 Research-status Report 2014 Research-status Report
  • [Remarks] 東京薬科大学 薬学部 病態生化学

    • URL

      http://www.ps.toyaku.ac.jp/~nomizu/

    • Related Report
      2015 Research-status Report 2014 Research-status Report
  • [Patent(Industrial Property Rights)] 抗癌剤2015

    • Inventor(s)
      吉川大和、福原武志、野水基義、伊東祐二
    • Industrial Property Rights Holder
      東京薬科大学、鹿児島大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-230926
    • Filing Date
      2015-11-26
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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