Molecular mechanism of malignat alteration in oral squamous cell carcinoma-development of approach to therapy and function analysis using siRNA-
| Project/Area Number |
18592215
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Department of Clinical Research, National Hospital Organization Kanazawa Medical Center (2007)
Kanazawa University (2006) |
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Principal Investigator |
NOZAKI Shinichi Department of Clinical Research, National Hospital Organization Kanazawa Medical Center, Clinical Research, Researcher (10283110)
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| 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)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | oral squamous cell carcinoma / uPA / uPAR / RNA interference / siRNA / cancer invasion / 口腔扁平上皮 / uPAR |
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| 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.
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Report
(3 results)
Research Products
(16 results)
