The role of urokinase-type plasminogen activator and its inhibitor PAI-1 in gastric cancer

Abstract

Background: It has been proposed that the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) may play an important part in cancer spread and metastasis.

Aims of the study: 1. To determine the UPA, PAI-1 antigen levels in gastric cancer (GC) and in normal gastric mucosa far from the tumor (NORM). 2. To evaluate changes related to the presence of metastasis, tumor differentiation (grading) and histotype.

Patients and methods: Samples of tumor and of normal mucosa were obtained from 25 GC patients undergoing surgery (17 males, 8 females, mean age 62, range 31-84). Antigen concentrations were measured using the ELISA method.

Results: Significantly higher UPA and PAI-1 antigen levels were found: 1. in GC vs. NORM tissue; 2. in patients with poorly and moderately differentiated GC vs. well-differentiated GC. UPA was significantly higher in GC with vs. without metastasis. PAI-1 was also higher, though not significantly so, in GC with metastasis than in GC without metastasis.

Conclusion: Our results confirm that the serine protease UPA and its inhibitor PAI-1 play an important role in GC progression. Considering the higher protease levels detected in GC with metastases and poorer differentiation, UPA and PAI-1 might be useful for identifying gastric cancer patients with a poor prognosis.