MELANOMA CELL-MIGRATION ON VITRONECTIN - REGULATION BY COMPONENTS OF THE PLASMINOGEN ACTIVATION SYSTEM

Tumor cell migration and invasion require complex interactions between tumor cells and the surrounding extracellular matrix. These interacti ons are modified by cell adhesion receptors, as well as by proteolytic enzymes and their receptors. Here, we study the influence of the prot ease urokinase-type plasminogen activator (uPA) and its receptor (uPAR ) on melanoma cell adhesion to, and migration on, the extracellular ma trix protein vitronectin (VN). Cell adhesion to VN, but not to type I collagen, is significantly enhanced in the presence of either uPA or i ts amino-terminal fragment (ATF). Soluble uPAR can inhibit this effect , indicating that uPA/uPAR on melanoma cells can function as a VN rece ptor. In the absence of bivalent cations, uPA/uPAR can promote cell at tachment on VN, but not cell spreading, suggesting that the glycosylph osphatidylinositol (GPI)-anchored uPAR alone is unable to organize the cytoskeleton. Chemotactic melanoma cell migration on a uniform VN mat rix is inhibited by uPA and ATF, implying that cell motility decreases when uPA/uPAR acts as a VN receptor. In contrast, plasminogen activat or inhibitor I (PAI-1) can stimulate melanoma cell migration on VN, pr esumably by inhibiting uPA/uPAR-mediated cell adhesion to VN and there by releasing the inhibition of cell migration induced by uPA. Together , our data implicate components of the plasminogen activation system i n the direct regulation of cell adhesion and migration, thereby modula ting the behavior of malignant tumor cells. (C) 1997 Wiley-Liss, Inc.