EXPRESSION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR RECEPTOR AND PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN GASTRIC-CANCER

In gastric cancer, the urokinase-type plasminogen activator (uPA) syst em plays important roles in invasion and metastasis, processes which e ntail proteolysis and adhesion. Both the urokinase-type plasminogen ac tivator receptor (uPAR) and the plasminogen activator inhibitor-1 (PAI -I) are thought to be important factors in this system. To clarify the relationship between these two factors and gastric cancer invasivenes s, we evaluated the expression of uPAR and PAI-I in 91 cases of gastri c cancer by immunohistochemistry and in situ hybridization. Urokinase- type plasminogen activator receptor-mRNA, PAI-1-mRNA, uPAR and PAI-1 p rotein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci. Urokinase-type plasminogen activat or receptor protein expression correlated with lymphatic, venous invas ion (P<0.01) and lymph node metastasis (P<0.05); uPAR-mRNA expression correlated with lymphatic, venous invasion and lymph node metastasis ( P<0.05). Plasminogen activator inhibitor-1 protein expression correlat ed with lymphatic, venous invasion, lymph node metastasis and depth of invasion (P<0.01); PAI-1-mRNA expression was linked to lymphatic, ven ous invasion (P<0.01), lymph node metastasis and depth of invasion (P< 0.05). This suggests that the proteolytic activity of uPAR and the cel lular motility of PAI-1 in gastric cancer cells may determine penetrat ion of lymphatic and blood vessels, whereby lymph node metastasis may be promoted and that the promotion of cellular motility by PAI-1 may i nfluence the depth of cancer invasion.