[Cellular proteases and invasion]

Cellular proteases are those proteases that are localized in the cytoplasm and on the cell surface, but not those secreted into the extracellular matrix. Proteases localized on the cell surface play a specific role in the invasion process of malignant tumor cells. These are activated by a relatively complicated cascade in which different cathepsins, the plasminogen activator system, plasmin, and the matrix metalloproteinases, including the membrane-type matrix metalloproteinases, play a major role. This article places emphasis on the biologic function and oncologic significance of cathepsins B and L, as well as on the urokinase plasminogen activator and the membrane-type matrix metalloproteinases localized on the cell surface. Recent investigations on these factors revealed that they are dependent on each other, such that the upregulation or downregulation also causes alterations in the regulation of the other factors. This fact alone elucidates the complexity of this system. Moreover, there is growing evidence that other proteases hitherto known to have other functions, e.g. as signal proteases in the immunologic system, may be important for invasion provesses. To provide an example of this, we describe the invasive potential of aminopeptidase N (APN/CD13). These recent results, which shed light on the role of further proteases in invasion processes, clearly show the complexity of this proteolytic system. Against this biologic background, it seems not to be promising to establish single proteases as distinct parameters for the prognosis of the metastatic potential of malignant tumors.