The Role of Proteases in Tumor Invasion and Metastasis: Prognostic Impact and Therapeutical Challenge?

Abstract

The capacity of solid tumors to invade surrounding tissue and to metastasize 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 metastasis. Four different classes of proteases are involved: 1. serine proteases, 2. metalloproteases, 3. cysteine proteases, and 4. aspartyl proteases. It has been shown that the content of some tumor-associated proteolytic factors in tumor extracts have a strong prognostic value. Especially the urokinase-type plasminogen activator (uPA) and the plasminogen activator inhibitor type-1 (PAI-1), predicting relapse-free and overall survival of patients with breast, gastric and ovarian cancer, allow to classify high-risk cancer patients. A prospective clinical study currently investigates whether lymph-node-negative breast cancer patients with either high uPA and/or PAI-1 level will benefit from adjuvant chemotherapy. Based on the present knowledge of basic and clinical aspects of tumor-associated proteases, new potential therapeutic strategies have emerged targeting these proteolytic enzyme systems.

Inhibition of tumour cell invasion by protease inhibitors: correlation with the protease profile

“…Autoactivation of pro-proteases has also been observed (Mach et al 1993;Menard et al 1998). The series of events is best described by an activation cascade ®rst suggested by Wilhelm et al (1994).…”