Fibrinolytic factors, matrix metalloprotease-1, and tissue inhibitor of metalloproteinase-1 in gastric carcinoma

Abstract

The invasion and metastasis of carcinoma cells require the action of tumor-associated proteases and their inhibitors, which may also may be involved in the stages of carcinogenesis. In the present study, we evaluated the levels of fibrinolytic factors, urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1), and u-PA specific receptor (u-PAR) as well as matrix metalloprotease-1 (MMP-1) and its tissue inhibitor of metalloprotease-1 (TIMP-1) in extracts of human gastric carcinoma tissues and their corresponding normal mucosas. The antigen levels of u-PA, PAI-1, and TIMP-1 were significantly higher in carcinomas than normal mucosas, while those of u-PAR were not changed as much. Thus, the increase of u-PAR ligand u-PA and its inhibitor PAI-1 may be important in carcinoma tissues. In addition, the amidolytic activity with S-2444 of carcinomas was significantly higher than that of normal tissue indicating that u-PA but not t-PA was involved in the fibrinolytic activity of carcinoma tissues. However, the relationships between any two factors among these components were not clear. From these findings, it is also confirmed that u-PA and PAI-1 are the major regulators of human gastric cancer cells. In addition, since both MMP-1 and TIMP-1 were found to be higher in the carcinomas than the normal mucosas, it is suggested that this matrix enzyme and inhibitor are also up-regulated in carcinomas, the pathway of which is independently linked to fibrinolytic system.