TPA and PAI-1 in malignant tissues of gastric adenocarcinoma can be tumor-associated.

Abstract

e15533 Background: Plasminogen regulator system is considered to be involved in migration, invasion and proliferation of malignant cells. The role of tissue plasminogen activator (tPA) and PAI-1 in cancer is still discussed. Our purpose was to study the antigen and active forms of tPA and PAI-1 (tPA-Ag, tPA-act and PAI-1-Ag, PAI-1-act) in tissues of gastric adenocarcinoma (GA), greater omentum and peritoneum with and without metastases (mts). Methods: We studied tissues of patients with GA T3-4аN0-3M1 (n = 21, 10 men, 11 women) and T3-4аN0-3M0 (n = 24, 15 men, 9 women) aged 61.23±4.8 years. Control group included 17 non-cancer patients aged 39.1±3.2 years (6 men, 11 women). Levels of tPA-act, tPA-Ag, PAI-1-act and PAI-1-Ag were measured by ELISA using standard test systems. Statistical analysis was performed using the SPSS 11.5 software package for Windows. Results: Levels of both forms of tPA and PAI-1 in GA with and without mts were 1-2 orders of magnitude higher than in resection line tissues. Levels of tPA-Ag and PAI-1-Ag in GA without mts were 1.7 and 2.5 times higher than in GA with mts, while levels of tPA-act and PAI-1-act were similar. In tissues of the greater omentum, levels of tPA-Ag with mts exceeded that in tissues without mts and in controls by 5.0 and 1.7 times, respectively; levels of tPA-act were similar to controls, while without mts they were 1.6 times lower than in controls. PAI-1-Ag with mts was 3.2 and 4.5 without mts and in controls, respectively; PAI-1-act with mts was 1.8 and 1.5 times higher than in controls and without mts, respectively. In tissues of the peritoneum, tPA-Ag with mts was 1.6 and 1.4 times higher than without mts and in controls, respectively; tPA-act with and without mts was 1.4 (p = 0.0412) and 1.5 times lower than in controls. PAI-1-Ag in the peritoneum with and without mts 1.4 times (p = 0.0428) exceeded control, and PAI-1-act was higher than in controls by 1.6 and 2.8 times, respectively. The results demonstrated that GA with and without mts secreted PAI-1 and tPA, and levels of tPA-Ag and both forms of PAI-1 were elevated in tissues of the peritoneum and omentum with and without mts. Conclusions: Levels of tPA-Ag and both forms of PAI-1 in the greater omentum and peritoneum without mts indicate possible formation of a pre-metastatic niche.