Cysteine and serine proteases in gastric cancer

Abstract

Background. Cysteine proteases (cathepsin B [CATB] and cathepsin L [CATL]), the serine protease urokinasetype plasminogen activator (UPA), and plasminogen activator inhibitor type‐1 (PAI‐1) are thought to play an important part in cancer invasion and metastasis. The aims of this study were to measure CATB, CATL, UPA, and PAI‐1 in gastric cancer (GC) and normal mucosa distant from the tumor (NORM); to evaluate whether tissue levels are related to tumor stage, grade, or histotype; to assess their prognostic relevance; and to examine UPA and PAI‐1 expression immunohistochemically. Methods. Gastric cancer and NORM samples were obtained from 25 patients with gastric cancer patients undergoing surgery (17 males, 8 females; mean age, 62 years; range, 31–84 years). Antigen concentrations were measured using the enzyme‐linked immunosorbent assay method. Immunohistochemistry was performed using monoclonal UPA and PAI‐1 antibodies. Results. Significantly higher antigen levels were found: (1) in GC vs. NORM (CATB, CATL, UPA, PAI‐1) tissues; (2) in GC with versus without metastasis (CATB, CATL, UPA); (3) in poorly or moderately versus well differentiated GC; and (4) in diffuse versus intestinal‐type GC (CATB, CATL). Urokinase‐type plasminogen activator, PAI‐1 and CATB levels had a significant prognostic impact. Cancer and stromal cells, showed immunoreactivity to anti‐UPA and anti‐PAI‐1 antibodies. Conclusions. These results confirm the important role of CATB, CATL, UPA and PAI‐1 in gastric cancer progression. Higher levels are detected in GC with metastases, poorer differentiation, and diffuse histotype, thus identifying patients with a worse prognosis Cancer 1995; 76:367–75. Copyright © 1995 American Cancer Society