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Evaluation of the role of TRAIL induced cell migration and invasion in cholangioma cells

Research Project

Project/Area Number 18590733
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionShimane University

Principal Investigator

ISHIMURA Norihisa  Shimane University, Faculty of Medicine, assistant professor (40346383)

Co-Investigator(Kenkyū-buntansha) ISHIHARA Shunji  Shimane University, Faculty of Medicine, associate professor (80263531)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,470,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordscancer / Cholangiocarcinoma / apoptosis / invasion / TRAIL
Research Abstract

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) induces apoptosis in various cancer cells but not in normal tissues through TRAIL receptors DR4 and DR5. Although many cancers including cholangiocarcinoma are resistant to TRAIL-mediated apoptosis, the mechanisms remain obscure. Thus our aim was to elucidate the cellular mechanisms by which TRAIL promotes cell migration and/or invasion in human cholangiocarcinoma cells.
Results
1. TRAIL protein was enhanced in cholangiocarcinoma tissues, but not normal tissues. TRAIL receptor protein expression was not enhanced in cholangiocarcinoma. Among the apoptotic related agents, Mc1-1 protein expression was significantly enhanced in cholangiocarcinoma. In cholangiocarcinoma cell lines, TRAIL protein was also enhanced as compare to immortalized cholangiocytes.
2. The differences of promoter sequences in TRAIL between normal and choangiocarcinoma was not detected.
3. TRAIL promoted tumor cell migration and invasion in cholangiocarinoma cells. TRAIL-mediated cell migration and invasion was NF-KB and Mcl-1 dependent. Cholangiocarcinoma cells transfected with TRAIL siRNA could potentially decrease cell migration and invasion. In conclusion, TRAIL potently stimulates tumor cell migration and invasion in cholangiocarcinoma cells and inhibition of Mcl-1 and NF-KB reduces TRAIL-mediated cell migration and invasion. Although TRAIL is being promoted as a promising anticancer drug, TRAIL-mediated invasiveness of apoptosis resistant cancer cells may restrict its use to apoptosis-sensitive tumors. The combination of TRAIL and inhibitors of Mcl-1 and/or NF-KB may be useful for apoptosis resistant cholangiocarcinoma cell

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (14 results)

All 2008 2007 2006

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (2 results)

  • [Journal Article] Prolactin induces MFG-E8 production in macrophages via transcription factor C/EBP beta-dependent pathway.2008

    • Author(s)
      Aziz MM
    • Journal Title

      Apoptosis (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] REG Ialpha protein expression in Barrett's esophagus2008

    • Author(s)
      Chinuki D
    • Journal Title

      J Gastroenterol Hepatol 23

      Pages: 296-302

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Prolactin induces MEG-E8 production in macrophages via transcription factor C/EBPbeta-dependent pathway2008

    • Author(s)
      Aziz, MM., Ishimura, N., et. al.
    • Journal Title

      Apoptosis (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] REG Ialpha protein expression in Barrett's esophagus2008

    • Author(s)
      Chinuki, D., Ishimura, N., et. al.
    • Journal Title

      J Gastroenterol Hepatol

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Predictors for squamouse re-epithelialization of Barrett's esophagus after endoscopic biopsy2007

    • Author(s)
      Amano Y
    • Journal Title

      J Gastroenterol Hepatol 22

      Pages: 901-907

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Predictors for squamous re-epithelialization of Barrett's esophagus after endoscopic biopsy2007

    • Author(s)
      Amano, Y., Ishimura, N., et. al.
    • Journal Title

      J Gastroenterol Hepatol

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Increased expression of midkine in the rat colon during healing of experimental colitis2006

    • Author(s)
      Yuki T
    • Journal Title

      Am J Physiol Gastointest Liver Physiol 291

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Prevalence of and risk factors for Barrett's esophagus with intestinal predominant mucin phenotype2006

    • Author(s)
      Amano Y
    • Journal Title

      Scnad J Gastroenterol. 41

      Pages: 873-879

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Evaluation of modified crystal violet chromoendoscopy procedure using new mucosal pit pattern classification for detection of Barrett's dysplastic lesions.2006

    • Author(s)
      Yuki T
    • Journal Title

      Dig Liver Dis. 38

      Pages: 296-300

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Increased expression of midkine in the rat colon during healing of experimental colitis2006

    • Author(s)
      Yuki, T., Ishimra, N., et. al.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Prevalence of and risk factors for Barrett's esophagus with intestinal predominant mucin phenotype2006

    • Author(s)
      Amano, Y., Ishimura, N., et. al.
    • Journal Title

      Scand J Gastroenterol

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Evaluation of modified crystal violet chromoendoscopy procedure using new mucosal pit pattern classification for detection of Barrett's dysplastic lesions2006

    • Author(s)
      Yuki, T., Ishimura, N., et. al.
    • Journal Title

      Dig Liver Dis

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Does aging extend Barrett's esophagus naturally?2007

    • Author(s)
      Amano Y
    • Organizer
      ASGE
    • Place of Presentation
      Washington, USA
    • Year and Date
      2007-05-20
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Does aging extend Barrett's esophagus naturally?2007

    • Author(s)
      Amano, Y
    • Organizer
      ASGE annual meeting
    • Place of Presentation
      Washington, USA
    • Year and Date
      2007-05-20
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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