Dissemination of tumor cells includes several steps, such as: (a) detachment of tumor cells from the primary tumor, (b) traversement of the basement membrane, and (c) migration into the extracellular matrix. In these processes, at least two important categories of proteins are involved: proteases and adhesion molecules. In this contribution we describe the expression and function of components of the plasminogen activator (PA) system (proteases) and of integrins (cell-matrix adhesion molecules) in a panel of four human melanoma cell lines with different invasive and metastatic capacity. Regarding the components of the PA system, we found differences in expression of urokinase-type PA (uPA) and type 1 and 2 PA inhibitors (PAI-1 and -2) between metastasizing and nonmetastasizing cell lines. Both components were exclusively expressed in the highly invasive and metastatic cell lines. Interestingly, studies on the expression of PA components in fresh human melanocytic lesions, showed expression of these components exclusively in advanced primary melanomas and melanoma metastases. Regarding integrin expression we found elevated levels of VLA-2 and VLA-6 in the highly invasive and metastatic cell lines compared with normal cultured melanocytes and nonmetastatic melanoma cell lines. In addition, increased adhesion of the highly metastatic cell lines to laminin (LM) and collagen (COLL) was observed. Furthermore, reduced adhesion of normal melanocytes and nonmetastatic melanoma cells to LM and CO was mainly due to the fact that the integrins involved in adhesion to these matrix components were present in an inactive state. Finally, differences were observed in expression of integrins involved in adhesion to fibronectin.