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2006 Fiscal Year Final Research Report Summary

Therapeutic approaches, including molecularly targeted therapies The inhibition of invasion and metastasis of oral cancers by molecularly targeted therapies Search for novel therapy and molecular pathogenesis of oral cancer metastasis

Research Project

Project/Area Number 16390593
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionKyushu University

Principal Investigator

SHIRASUNA Kanemitsu  Kyushu University, Graduate School Dental Science, Professor, 大学院歯学研究院, 教授 (30093420)

Co-Investigator(Kenkyū-buntansha) SUGIURA Tuyoshi  Kyushu University, Hospital, Research Associate, 大学病院, 助手 (40322292)
Project Period (FY) 2004 – 2006
KeywordsOral cancer / uPA / uPAR / integrin / tumor invasion / metastasis / VEGF
Research Abstract

The prognosis of patients with oral cancer is influenced by the presence of metastasis. Understanding the molecular pathogenesis of oral cancer metastasis may lead to a rational development of new therapies. The present study has demonstrated several molecules that could serve as targets for novel therapy. Although mechanism of metastasis remains unclear, tumor cells must migrate through the extracellular matrix (ECM) in order to invade local tissues and metastasize to distal sites. Migrating cells use both adhesion molecules and proteolytic enzymes to regulate their interaction with and response to ECM. One of the most important proteolysis systems is urokinase-type plasminogen activator (uPA)/ uPA receptor (uPAR)/plasmin. The expression levels of uPA and uPAR have been related to invasion and metastasis and a poor survival rate. uPA bound to uPAR exhibits enhanced proteolytic activity and directly activates plasminogen, matrix metalloproteases, which gives rise to enhanced ECM degrad … More ation. The uPA-uPAR interaction also mediates several signal events, regulates cell adhesion, modulates integrin activity, and triggers cell migration. The expression of uPA-uPAR is regulated by activation of AP-1 and NFκ-B, and inhibition of either AP-1 or NFκ-B with decoy system suppresses tumor invasion of oral cancer cells.
Adenoid cystic carcinoma (AdCC) is characterized by nerve and vascular invasion and frequent distant metastasis. Cell lines, such as ACCS, from AdCC have high surface level of uPAR and show high migration response to collagens, and this response is exclusively inhibited by the anti-a2 integrin antibody. On the collagens, AdCC form numerous focal adhesion consisting of uPAR, vincullin and paxillin. ACCS-AS cell line transfected with a vector expressing antisense uPAR RNA showed strong reduction of collagen-stimulated migration and focal adhesion assembly, suggesting that uPAR plays a key role in tumor invasion.
In addition, our study suggest that vascular endothelial growth factor (VEGF)-C and VEGF-D and the tetraspanin KAI-1/CD82 could serve as molecularly targeted therapy for oral cancer. Less

  • Research Products

    (16 results)

All 2005 2004

All Journal Article (16 results)

  • [Journal Article] Expression of the urokinase receptor regulates focal adhesion assembly and cell migration in adenoid cystic cartinoma cells2005

    • Author(s)
      Abu-AliS., Sugiura T., Takahashi M., Shiratsuchi T., Ikari T., Seki K., Hiraki A., matuki R., Shirasuna K.
    • Journal Title

      J. Cell Physiol. 203

      Pages: 410-419

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differentiation-inducing factor-1 induces cyclin D1 degradation through the phosphorylation of Thr(286)in squamous cell carcinoma.2005

    • Author(s)
      Mori J, Takahashi-Yanaga F, Miwa Y, Watanabe Y, Hirata M, Morimoto S, Shirasuna K, Sasaguri T
    • Journal Title

      Exp. Cell Res.

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effects of I κB kinase α on the differentiation of squamous carcinoma cells.2005

    • Author(s)
      Nakayama H, Ikebe T, Shirasuna K.
    • Journal Title

      Oral Oncol 41

      Pages: 729-737

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] An adenoid cystic carcinoma NF- κB activation in response to TNF-α.2005

    • Author(s)
      Seki K, Ishii K, Sugiura T, Takahashi M, Inoue Y, Shirasuna K.
    • Journal Title

      Oral Sci Int. 2

      Pages: 36-44

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Adenoid cystic carcinoma : Participation of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in tumor invasion.2005

    • Author(s)
      Shirasuna K
    • Journal Title

      Oral Sci Int. 2

      Pages: 60-79

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of the urokinase receptor regulates focal adhesion assembly and cell migration in adenoid cystic carcinoma cells.2005

    • Author(s)
      Abu-Ali S, Sugiura T, Takahashi M, Shiratsuchi T, Ikari T, Seki K, Hiraki A, Matsuki R, Shirasuna K.
    • Journal Title

      J Cell Physiol 203

      Pages: 410-419

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Differentiation-inducing factor-1 induces cyclin D1 degradation through the phosphorylation of Thr(286) in squamous cell carcinoma.2005

    • Author(s)
      Mori J, Takahashi-Yanaga F, Miwa Y, Watanabe Y, Hirata M, Morimoto S, Shirasuna K, Sasaguri T.
    • Journal Title

      Exp Cell Res

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of IκB kinase a on the differentiation of squamous carcinoma cells.2005

    • Author(s)
      Nakayama H, Ikebe T, Shirasuna K.
    • Journal Title

      Oral Oncol 41

      Pages: 729-737

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] An adenoid cystic carcinoma NF-κB activation in response to TNF-α.2005

    • Author(s)
      Seki K, Ishii K, Sugiura T, Takahashi M, Inoue Y, Shirasuna K.
    • Journal Title

      Oral Sci Int. 2

      Pages: 36-44

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Adenoid cystic carcinoma : Participation of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in tumor invasion.2005

    • Author(s)
      Shirasuna K.
    • Journal Title

      Oral Sci Int. 2

      Pages: 60-79

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] NF-κB involvement in tumor-stroma interaction of squamous cell carcinoma.2004

    • Author(s)
      Ikebe T, Nakayama H, Shinohara M, Shirasuna K.
    • Journal Title

      Oral Oncology 40

      Pages: 1048-1056

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Integrin expression and migration of adenoid cystic carcinoma cells in response to basement membrane components.2004

    • Author(s)
      LiC-Y, Abu-Ali S., Sugiura T, Shiratsuchi T., Sasaki M, Shirasuna K.
    • Journal Title

      Oral Science International 1

      Pages: 22-29

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] T-cell receptor V βgene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma.2004

    • Author(s)
      Kumamaru W, Nakamura S, Kadena T, Yamada A, Kawamura E., Sasaki M., Ooyama Y., Toyosima T., Hayashida J., Itoh K., Shirasuna K.
    • Journal Title

      International J. Cancer 108

      Pages: 686-695

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] NFκ-B involvement in tumor-stroma interaction of squamous cell carcinoma.2004

    • Author(s)
      Ikebe T, Nakayama H, Shinohara M, Shirasuna K.
    • Journal Title

      Oral Oncology 40

      Pages: 1048-1056

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Integrin expression and migration of adenoid cystic carcinoma cells in response to basement membrane components.2004

    • Author(s)
      Li C-Y, Abu-Ali S, Sugiura T, Shirathuti T, Sasaki M, Shirasuna K.
    • Journal Title

      Oral Sci Int 1

      Pages: 22-29

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] T-cell receptor V β gene usage by T cells reactive with the tumor-rejection antigen SART-1 in oral squamous cell carcinoma.2004

    • Author(s)
      Kumamaru W, Nakamura S, Kadena T, Yamada A, Kawamura E, Sasaka M, Ohyama Y, Toyoshima T, Hayashida J, Itoh K, Shirasuna K.
    • Journal Title

      Int J Cancer 108

      Pages: 686-695

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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