| Project/Area Number |
12307049
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Kyushu University |
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Principal Investigator |
SHIRASUNA Kanemishu Graduate School Dental Science, Professor, 大学院・歯学研究院, 教授 (30093420)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIURA Toyoshi Faculty of Dentistry, Assistant Professor, 歯学部附属病院, 助手 (40322292)
ISHIBASHI Hiroaki Graduate School Dental Science, Assistant Professor, 大学院・歯学研究院, 助手 (90254630)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥43,050,000 (Direct Cost: ¥36,900,000、Indirect Cost: ¥6,150,000)
Fiscal Year 2002: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2001: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2000: ¥16,400,000 (Direct Cost: ¥16,400,000)
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| Keywords | oral cancer invasion / u-PA / uPAR / EGF / TNF-α / dexamethasone / AP-1 / NK-Κ B / ウロキナーゼ型プラスミノーゲンアクチベター / 悪性新生物 / 血管新生 / 基質破壊酵素 / 浸潤・転移 / プロテアーゼ / 転写因子 / 浸潤抑制 |
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| Research Abstract |
Investigation of molecular mechanism of cancer invasion and metastasis is important for development of new cancer therapy. Invasive squamous cell carcinoma (SCC) cells degrade extracellular matrix (ECM) via an extracellular protease cascade that includes urokinase-type plasminogen activator (uPA), plasmin, and the metalloprotease (MMP) family of collagenases. The treatment of oral SCC cells with epidermal growth factor (EGF) or TNF- α stimulated the cells to invade Matrigel. TNF- α stimulated MMP-9 production and activation mediated by increased uPA expression through NF Κ B activation. DEX inhibited TNF- α -induced changes including invasion, MMP-9 and uPA expression, as well as NF Κ B activation. EGF induced increased expression of uPA and uPA receptor (uPAR) proteins and mRNA, as well as activation of AP-1. These EGF-induced changes were inhibited by treatment with dexamethasone (DEX). DEX treatment also stimulated the production of plasminogen activator inhibitor type 1. Moreover, transfection of SCC cells with AP-1 decoy oligodeoxynucleotides resulted in the suppression of EGF-induced uPA and uPAR expression and Matrigel invasion. These results suggest that AP-1 and NF Κ B are one of targets for inhibiting tumor invasion. DEX, which inhibits both AP-1 and NF Κ B, may be a useful treatment for oral SCC.
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