Abstract
e15530 Background: Peritoneal metastases are the most common recurrence of gastric cancer, even after radical surgery. Urokinase-type plasminogen activator (uPA) system, including its receptor uPAR, is crucial in the proteolysis activation for the cleavage of the extracellular matrix and basement membrane. The purpose of the study was to determine the antigen form uPA-Ag, active form uPA-act and the uPAR receptor in tissues of adenocarcinoma of the stomach, its perifocal tissues (PT), greater omentum and peritoneum in patients with stomach cancer T3-4аN0-3M1 and T3-4аN0-3M0. Methods: Tissues of patients with gastric adenocarcinoma 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 were studied. Controls: non-cancer patients aged 39.1±3.2 years (n = 17: 6 men, 11 women). Levels of uPA-act, uPA-Ag and uPAR were determined by ELISA using standard test systems. Statistical analysis was performed using the SPSS 11.5 software package for Windows. Results: In T3-4аN0-3M1, the highest uPAR levels were observed in tissues of the tumor, greater omentum and peritoneum, compared to T3-4аN0-3M0 and controls (p < 0.01). In PT of T3-4аN0-3M1, uPAR levels were lower than in tumor (p < 0.01) but higher than in resection line tissues. Tumor levels of uPA-act in T3-4аN0-3M1 and T3-4аN0-3M0 were similar and in both cases higher than in PT. In the greater omentum in T3-4аN0-3M1, uPA-act levels were similar to tumor levels and exceeded the values in T3-4аN0-3M0 (p < 0.01). Peritoneal uPA-act did not differ in T3-4аN0-3M1 and T3-4аN0-3M0 but was higher than in controls (p < 0.05). Tumor levels of uPA-Ag in T3-4аN0-3M1 exceeded the levels in T3-4аN0-3M0 and in both PT (p < 0.05). Levels of uPA-Ag in the greater omentum in T3-4аN0-3M1 were higher than in T3-4аN0-3M0 and lower than in controls (p < 0.01). Comparable uPA-Ag levels in T3-4аN0-3M1 and T3-4аN0-3M0 were lower than in controls (p < 0.01). Conclusions: Gastric adenocarcinoma secretes uPAR and uPA, and uPAR levels in the tumor are associated with omental or peritoneal metastases. Levels of uPAR and uPA-act in the greater omentum and peritoneum in T3-4аN0-3M1 are increased even higher than in T3-4аN0-3M0; uPAR can serve as a marker of a pre-metastatic niche in peritoneal tissues.
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