2006 Fiscal Year Final Research Report Summary
Experimental study on the inhibition of invasion and metastasis of oral cancer by the suppression of processing of E-cadherin
| Project/Area Number |
17592083
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
HAYASHIDO Yasutaka Hiroshima University, Hospital, Assistant Professor, 病院, 講師 (70243251)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIOKA Yukio Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院医歯薬学総合研究科, 助手 (20335665)
KOBAYASHI Masashi Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院医歯薬学総合研究科, 助手 (30346506)
KOIZUMI Koh-ichi Hiroshima University, Hospital, Research Associate, 病院・助手 (30335682)
OKAMOTO Tetsuji Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (00169153)
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| Project Period (FY) |
2005 – 2006
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| Keywords | oral cancer / invasion and metastasis / E-cadherin / processing / plasminogen / plasmin / cell aggregation / cell migration |
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| Research Abstract |
The participation of plasminogen activator/plasmin system in the expression and function of E-cadherin was examined in oral squamous cell carcinoma (SCC) cells. Treatment of SCC cells with plasminogen reduced the Ca^<2+>-dependent cell aggregation. SCC cells expressed E-cadherin at the cell membrane, and released a small amount of soluble E-cadherin at 80 kDa in the culture medium. Addition of plasminogen to SCC cells led to a decrease in the amount of E-cadherin of the cell membrane and the enhancement of the shedding of E-cadherin ectodomain. Plasmin directly cleaved E-cadherin of SCC cells and enhanced the motility of SCC cells. These results suggested that plasminogen activator/plasmin system might directly mediate the proteolytic processing of E-cadherin in oral SCC cells and that might facilitate the progression of oral SCC by downregulation of E-cadherin-mediated cell-cell adhesion.
To examine the effect of downregulation of plasminogen activator/plasmin system by a2-antiplasmin (a2-AP) on cell-cell adhesion mediated by E-cadherin in oral SCC cells, the oral SCC cell line SCCKN was stably transfected with a2-AP cDNA. Induction of a2-AP expression led to the inhibition of the proteolysis of E-cadherin by plasminogen activator/plasmin in SCC cells, resulting in the enhancement of the cell aggregation and the suppression of the cell motility. Moreover, a2-AP also reduced the ability of SCC cells to invade type I collagen gel, and suppressed the tumorigenicity in vivo. These results suggested that downregulation of plasminogen activator/plasmin system by a2-AP might be a potent therapeutic approach to prevent the progression of oral SCC.
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