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.