Different Roles for Plasminogen Activators and Metalloproteinases in Melanoma Metastasis

Abstract

The architecture of normal tissues is maintained by interactions between cells and the extracellular matrix (ECM). In this cooperation, cells produce and assemble the components of the ECM whereas the ECM stabilizes the physical structure of tissues and also regulates the behavior of cells (McDonald 1988, Adams and Watt 1993). Transformed cells can alter the composition and structural integrity of adjacent matrix promoting tumor progression. Enzymes produced by tumor cells can degrade different components of the ECM, such as collagens, glycoproteins and proteoglycans, and such matrix-degrading enzymes were shown to contribute to tumor invasion and metastasis in various experimental systems (for review of the extensive literature see Mareel et al. 1991; Mignatti and Rifkin 1993). The current view emerging from these studies is that the concerted action of several different enzymes, whose activities are modulated by complex control mechanisms, is required in malignancy. The functional role of the enzymatic degradation of ECM by tumor cells has been thought to be the dissolution of occluding matrix, thus enabling the cells to invade into the interstitial matrix of the mesenchyme at the site of a primary tumor, to cross the basement membrane of blood vessels in the process of intra- and extravasation and lastly to invase into the mesenchyme of a secondary site. More recently, it has been recognized that enzymatically altered matrix also provides a complex source of molecular information that can modulate tumor cell behavior including adhesion, survival, growth and migration.