THE ROLE OF PROTEASES IN TUMOR INVASION AND METASTASIS - PROGNOSTIC IMPACT AND THERAPEUTIC CHALLENGE

The capacity of solid tumors to invade surrounding tissue and to metas tasize is correlated with the formation and degradation of structural elements in the vicinity of the tumor cells. Evidence has accumulated that proteases play a crucial role in tumor cell invasion and metastas is. Four different classes of proteases are involved: 1. serine protea ses, 2. metalloproteases, 3. cysteine proteases, and 3. aspartyl prote ases. It has been shown that the content of some tumor-associated prot eolytic factors in tumor extracts have a strong prognostic value. Espe cially the urokinase-type plasminogen activator (uPA) and the plasmino gen activator inhibitor type-1 (PAI-1), predicting relapse-free and ov erall survival of patients with breast, gastric and ovarian cancer, al low to classify high-risk cancer patients. A prospective clinical stud y currently investigates whether lymph-node-negative breast cancer pat ients with either high uPA and/or PAI-1 level will benefit from adjuva nt chemotherapy. Based on the present knowledge of basic and clinical aspects of tumor-associated proteases, new potential therapeutic strat egies have emerged targeting these proteolytic enzyme systems.