Tumor cell-mediated proteolysis: regulatory mechanisms and functional consequences

The mammalian organism is composed of an inter-dependent series of tissue c ompartments separated from each other by an extracellular matrix (ECM). Thi s ECM functions as both a determinant of tissue architecture and a mechanic al barrier to cellular invasion. ECM proteolysis facilitates tissue penetra tion, and a distinctive property of many malignant tumor cells is the capac ity to invade host tissues and establish metastatic foci. Malignant cells p roduce a spectrum of matrix-degrading proteinases with activities directed against the major ECM proteins. These enzymes are identical to those normal ly involved in physiologic processes; however, proteinase regulation is alt ered such that enzyme expression and/or activity are inappropriately contro lled. The purpose of this review is to highlight biochemical mechanisms com monly utilized by tumor cells to regulate proteinase activity and to discus s the potential functional consequences with respect to tumor cell behavior . Specific examples will be provided to illustrate the concepts of regulati on via limited proteolysis, enzyme-inhibitor binding, compartmentalization, and alteration of proteinase expression. (C) 2000 Harcourt Publishers Ltd.