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2007 Fiscal Year Final Research Report Summary

Molecular mechanism of malignat alteration in oral squamous cell carcinoma-development of approach to therapy and function analysis using siRNA-

Research Project

Project/Area Number 18592215
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionDepartment of Clinical Research, National Hospital Organization Kanazawa Medical Center (2007)
Kanazawa University (2006)

Principal Investigator

NOZAKI Shinichi  Department of Clinical Research, National Hospital Organization Kanazawa Medical Center, Clinical Research, Researcher (10283110)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Esuhide  Kanazawa University, Graduate School of Medical Science, Oral & Maxillofacial Surgery, Professor (00092445)
KAWASHIRI Shuich  Kanazawa University, Graduate School of Medical Science, Oral & Maxillofacial Surgery, Instructor (30291371)
Project Period (FY) 2006 – 2007
Keywordsoral squamous cell carcinoma / uPA / uPAR / RNA interference / siRNA / cancer invasion
Research Abstract

Several proteolytic enzyme systems, involving plasminogen activators (PAs), matrix metalloproteinases (MMPs) and other enzymes, are thought to be intimately involved in invasion and metastasis of tumor cells. Urokinasc-type PA (uPA), which plays an essential role in conversion of PA to active plasmin and proteolysis of extracellular matrix (ECM), has been implicated in cancer cell invasion and metastasis. In particular, the activity of receptor (uPAR)-bound uPA is an important factor in the degradation ECM. There have been reports of strong correlations between poor prognosis in various cancers and concomitant expression of urokinase-type plasminogen activator (uPA) and its surface receptor (uPAR). We and others have previously shown that the uPA system plays a significant role in a subset of head and neck squamous cell carcinoma. Additionally, we found that uPAR is required for invasion and metastasis of highly malignant oral cancer cells. Treating cells with antisense oligonucleotides (AS) targeting uPAR resulted in a dramatic decrease of uPAR mRNA expression. Pretreatment with AS targeting uPAR inhibited progression of oral cancer cells in experimental models. In the present research, transfection of cells with uPAR siRNA resulted in a dramatic decrease of uPAR mRNA expression and fibronectin degradationin in fibronectin degradation/invasion assays. Fibronectin degradation was not affected by transfection of nonsense siRNA. These results suggest that overexpression of uPAR increases the invasiveness and metastasis of cells derived from oral squamous cell carcinoma, and that uPAR is a promising therapeutic target for regulation of progression of oral cancer.

  • Research Products

    (8 results)

All 2008 2007

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (2 results)

  • [Journal Article] Immunohistocheraical expressions of E-cadherin and beta-catenln correlate with the invasion, metastasis and prognosis of oral squamous cell carcinoma2008

    • Author(s)
      Hiroko Kitahara
    • Journal Title

      Oral Surg 1

      Pages: 28-34

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Immunohistochemical expressions of E-cadherin and beta-catenin correlate with the invasion, metastasis and prognosis of oral squamous cell carcinoma2008

    • Author(s)
      Hiroko Kitahara
    • Journal Title

      Oral Surg 1

      Pages: 28-34

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Copper efflux transporter (ATP7B)contributes to the acquisition of cisplatin-resistance in human oral squamous cell lines2007

    • Author(s)
      Kunio Yoshizawa
    • Journal Title

      Oncol Rep 18

      Pages: 987-991

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Expression of copper efflux transporter (ATP7B)in the transport of cisplatin in cell lines devived from invasive oral squamous cell carcinoma2007

    • Author(s)
      Kunio Yoshizawa
    • Journal Title

      Oral Sci Int 4

      Pages: 28-37

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Copper efflux transporter (ATP7B) contributes to the acquisition of cisplatin-resistance in human oral squamous cell lines2007

    • Author(s)
      Kunio Yoshizawa
    • Journal Title

      Oncol Rep 18

      Pages: 987-991

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of copper efflux transporter (ATP7B) in the transport of cisplatin in cell lines devived from invasive oral squamous cell carcinoma2007

    • Author(s)
      Kunio Yoshizawa
    • Journal Title

      Oral Sci Int 4

      Pages: 28-37

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] ウロキナーゼ型プラスミノーゲンアクチベーター受容体を標的とした口腔癌に対する治療戦略2007

    • Author(s)
      能崎 晋一
    • Organizer
      第61回NPO法人日本口腔科学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2007-04-19
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Targeting urokinase-type plasminogen activator receptor for oral cancer2007

    • Author(s)
      Shinichi Nozaki
    • Organizer
      61^<st> annual meeting of Japanese Stomatological Society
    • Place of Presentation
      Kobe
    • Year and Date
      2007-04-19
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-06-09  

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