Extracellular matrix production and degradation by adenoid cystic carcinoma cells : participation of plasminogen activator and its inhibitor in matrix degradation

Adenoid cystic carcinoma (AdCC) is characterized by low mitogenic activity, high invasiveness, and vigorous production and accumulation of extracellular matrix (ECM). As it does in vivo, a cell line (ACCS) derived from a human AdCC grows very slowly and displays potential for production of a large amount of ECM. ACCS cells also produce a significant amount of proteolytic enzymes, including urokinase-type plasminogen activator (uPA), and M(r) 72,000 and 92,000 gelatinases. These cells can degrade considerable amounts of ECM elaborated by normal mesenchymal cells, including rat muscle cells and human fibroblasts, mainly through a uPA-plasmin cascade. However, ECM elaborated by ACCS cells themselves is resistant to degradation by either the tumor cells or purified uPA in the presence of plasminogen, whereas the degradation rates of ACCS ECM and mesenchymal ECM by plasmin are comparable. Treatment of ECM with glycine (pH 2.7), which removes plasminogen activator inhibitor from the matrix, results in an increase in the rate of ACCS ECM degradation by uPA. Moreover, fibrin agarose reverse zymography, autoradiography, and immunoblotting showed a high level of plasminogen activator inhibitor type 1 in ACCS ECM. These findings suggest that the plasminogen activator inhibitor type 1 in ECM produced by AdCC cells may play a role in preventing matrix destruction by the tumor itself, and thus the ECM components of tumor origin are stably accumulated in the intercellular spaces and may support or promote the growth of AdCC cells, which have primitively low growth activity.