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Participation of Plasminogen Activator/Plasmin System in Cell-cell Adhesion and Invasive Growth of Oral Squamous Cell Carcinoma Cells

keywords_en.jpgPlasminogen Activator/Plasmin System, E-cadherin, α2-antiplasmin 

division_en.jpg Applied Life Sciences

position_en.jpg Assistant Professor

Outline

Background

The proteolytic activity and migration of cancer cells closely participate with tumor invasion and metastasis. It
is well known that the plasmin plays a main role in extracellular matrix (ECM) proteases, and regulates tumor
invasion and metastasis. In addition, it is indicated that the plasmin regulates the proteolytic processing and
affects the expression and function of cell membrane proteins. However, it isn’t being cleared a role of
plasminogen activator/plasmin system in the fragmentation, expression and function of E-cadherin which regulates cell-cell adhesion. I thought that if the plasmin suppresses the function of E-cadherin, impairs the intercellular adhesion and facilitates the cell migration of squamous cell carcinoma (SCC ) cells. Therefore, it
was suggested that the inhibition of plasmin activity not only suppresses the proteolytic activity but reduces the migration of cancer cells, and suppresses tumor invasion and metastasis.

Research Summary

The influence of plasminogen activator/plasmin system in the proteolytic processing, expression and function of
E-cadherin on oral SCC cells was investigated. Moreover, it was examined whether the induction of α2-antiplasmin (α2-AP) which is the plasmin inhibitor affects expression of E-cadherin and the cell aggregation and invasive growth of oral SCC cells.

Result

The plasmin cleaved the ectodomain of E-cadherin and reduced the cell aggregation and promotes the cell migration by downregulation of E-cadherin-mediated cell-cell adhesion in SCC cells. It was indicated that the induction of α2-AP suppressed E-cadherin processing by inhibit plasmin activity, and reduced the cell migration and invasive growth of SCC cells.

For Application

In vivo studies will be required to establish the safe and effective α2-AP protein expression system with simple injection of the α2-AP gene into oral SCC tissue.

Competitive Advances

It isn’t being cleared a role of plasminogen activator/plasmin system in the processing, expression and function of E-cadherin on SCC cells. The downregulation of the plasminogen activator/plasmin system by α2-AP might be a potent therapeutic approach to prevent the progression of oral SCC.

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International Journal of Oncology 27: 693-698, 2005.
Oncology Reports 17: 417-423, 2007

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