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Experimental study on the inhibition of invasion and metastasis of oral cancer by the suppression of processing of E-cadherin

Research Project

Project/Area Number 17592083
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

HAYASHIDO Yasutaka  Hiroshima University, Hospital, Assistant Professor, 病院, 講師 (70243251)

Co-Investigator(Kenkyū-buntansha) YOSHIOKA Yukio  Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院医歯薬学総合研究科, 助手 (20335665)
KOBAYASHI Masashi  Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院医歯薬学総合研究科, 助手 (30346506)
KOIZUMI Koh-ichi  Hiroshima University, Hospital, Research Associate, 病院・助手 (30335682)
OKAMOTO Tetsuji  Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (00169153)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsoral cancer / invasion and metastasis / E-cadherin / processing / plasminogen / plasmin / cell aggregation / cell migration / アンチプラスミン
Research Abstract

The participation of plasminogen activator/plasmin system in the expression and function of E-cadherin was examined in oral squamous cell carcinoma (SCC) cells. Treatment of SCC cells with plasminogen reduced the Ca^<2+>-dependent cell aggregation. SCC cells expressed E-cadherin at the cell membrane, and released a small amount of soluble E-cadherin at 80 kDa in the culture medium. Addition of plasminogen to SCC cells led to a decrease in the amount of E-cadherin of the cell membrane and the enhancement of the shedding of E-cadherin ectodomain. Plasmin directly cleaved E-cadherin of SCC cells and enhanced the motility of SCC cells. These results suggested that plasminogen activator/plasmin system might directly mediate the proteolytic processing of E-cadherin in oral SCC cells and that might facilitate the progression of oral SCC by downregulation of E-cadherin-mediated cell-cell adhesion.
To examine the effect of downregulation of plasminogen activator/plasmin system by a2-antiplasmin (a2-AP) on cell-cell adhesion mediated by E-cadherin in oral SCC cells, the oral SCC cell line SCCKN was stably transfected with a2-AP cDNA. Induction of a2-AP expression led to the inhibition of the proteolysis of E-cadherin by plasminogen activator/plasmin in SCC cells, resulting in the enhancement of the cell aggregation and the suppression of the cell motility. Moreover, a2-AP also reduced the ability of SCC cells to invade type I collagen gel, and suppressed the tumorigenicity in vivo. These results suggested that downregulation of plasminogen activator/plasmin system by a2-AP might be a potent therapeutic approach to prevent the progression of oral SCC.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (20 results)

All 2007 2006 2005

All Journal Article (19 results) Book (1 results)

  • [Journal Article] Developmental signaling disorders in craniofacial anomalies and cancer2007

    • Author(s)
      Zhang, Y
    • Journal Title

      Oral Science International 3(2)

      Pages: 417-423

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Induction of alpha2-antiplasmin inhibits E-cadherin processing mediated by the plasminogen activator/plasmin system, leading to suppression of progression of oral squamous cell carcinoma via upregulation of cell-cell adhesion2007

    • Author(s)
      Hayashido, Y.
    • Journal Title

      Oncol Rep. 17(2)

      Pages: 417-423

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Developmental signaling disorders in craniofacial anomalies and cancer2007

    • Author(s)
      Zang Y, et al.
    • Journal Title

      Oral Science International 3(2)

      Pages: 417-423

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Induction of alpha2-antiplasmin inhibits E-cadherin processing mediated by the plasminogen activator/plasmin system, leading to suppression of progression of oral squamous cell carcinoma via upregulation of cell-cell adhesion2007

    • Author(s)
      Hayashido, Y. et al.
    • Journal Title

      Oncol Rep. 17(2)

      Pages: 417-423

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Induction of alpha2-antiplasmin inhibits E-cadherin processing mediated by the plasminogen activator/plasmin system, leading to suppression of progression of oral squamous cell carcinoma via upregulation of cell-cell adhesion2007

    • Author(s)
      Hayashido Y
    • Journal Title

      Oncol Rep. 17・2

      Pages: 417-423

    • Related Report
      2006 Annual Research Report
  • [Journal Article] インテグリンβ8発現抑制が口腔扁平上皮癌細胞の増殖能と浸潤能に与える影響2006

    • Author(s)
      北野尚孝
    • Journal Title

      口腔組織培養学会誌 15・1

      Pages: 53-54

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Developmental signaling disorders in craniofacial anomalies and cancer2006

    • Author(s)
      Zang Y
    • Journal Title

      Oral Science International 3・2

      Pages: 56-63

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Plasminogen activator/plasmin system suppresses cell-cell adhesion of oral squamous cell carcinoma cells via proteolysis of E-cadherin2005

    • Author(s)
      Hayashido, Y
    • Journal Title

      Int. J. Oncol 27(3)

      Pages: 693-698

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas2005

    • Author(s)
      Zhang, Y
    • Journal Title

      Int. J. Cancer 117(1)

      Pages: 166-168

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Differentiation in adenoid cystic carcinoma of submaxillary gland : A case of report2005

    • Author(s)
      Hayashido, Y
    • Journal Title

      Oral Oncology EXTRA 41(5)

      Pages: 84-88

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Primary intraosseous carcinoma of mandible associated with elevation of serum carcinoembryonic antigen level : A case of report2005

    • Author(s)
      Hayashido, Y
    • Journal Title

      Oral Oncology EXTRA 41(10)

      Pages: 267-271

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Plasminogen activator/plasmin system suppresses cell-cell adhesion of oral squamous cell carcinoma cells via proteolysis of E-cadherin2005

    • Author(s)
      Hayashido, et al.
    • Journal Title

      Int.J.Oncol. 27(3)

      Pages: 693-698

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas2005

    • Author(s)
      Zhang, Y. et al.
    • Journal Title

      Int.J.Cancer 117(1)

      Pages: 166-168

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Differentiation in adenoid cystic carcinoma of submaxillary gland : A case of report2005

    • Author(s)
      Hayashido, Y. et al.
    • Journal Title

      Oral Oncology EXTRA 41(5)

      Pages: 84-88

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Primary intraosseous carcinoma of mandible associated with elevation of serum carcinoembryonic antigen level : A case of report2005

    • Author(s)
      Hayashido, Y. et al.
    • Journal Title

      Oral Oncology EXTRA 41(10)

      Pages: 267-271

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Plasminogen activator/plasmin system suppresses cell-cell adhesion of oral squamous cell carcinoma cells via proteolysis of E-cadherin2005

    • Author(s)
      Hayashido, Y
    • Journal Title

      Int.J.Oncol. 27(3)

      Pages: 693-698

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Constitutive activating mutation of the FGFR3b in oral squamous cell carcinomas2005

    • Author(s)
      Zhang, Y
    • Journal Title

      Int.J.Cancer 117(1)

      Pages: 166-168

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Dedifferentiation in adenoid cystic carcinoma of submaxillary gland : A case of report2005

    • Author(s)
      Hayashido, Y
    • Journal Title

      Oral Oncology EXTRA 41(5)

      Pages: 84-88

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Primary Leiomyosarcoma of the Mandible2005

    • Author(s)
      Yoshioka, Y
    • Journal Title

      Asian. J.Oral. Maxillofac. Surg. 17(2)

      Pages: 106-109

    • Related Report
      2005 Annual Research Report
  • [Book] 言語聴覚士のための基礎知識 臨床歯科医学・口腔外科学2006

    • Author(s)
      夏目長門編
    • Total Pages
      2
    • Publisher
      医学書院
    • Related Report
      2006 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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