Immobilized plasminogen activator inhibitor-1 (pai-1) mediates cell adhesion, spreading and cytoskeletal reorganization

We have shown previously that the urokinase receptor mediates force transmission across the cell surface (Wang et al., Am. J. Physiol., 268:01062. 1995). Here we investigated the further notion that immobilized plasminogen inhibitor-1 (PAI-1) could regulate cell spreading and cytoskeletal reorganization. Serum deprived human myogenic cells were plated in serum free medium into bactériologique 96-wells precoated with different extracellular matrix (ECM) ligands (fibroneclin, vitronectin, type I collagen) or PAI-1, at an increasing concentration (0, 0.225, 2.25, 4.5, 22.5, ng/well). The number of the adherent cells and their projected area were quantitated after 3 hours of plating. PAI-1 promoted cell adhesion and spreading in a dose dependant manner. Addition of antibody against PAI-1 also inhibited the adhesion on PAI-1 coated dishes in a dose dependent manner. However, adherent cells exhibited more filapodia on PAI-1 than on fibronectin coated dishes. These data suggest that PAI-1 plays a direct role in dynamic cell adhesion at the leading edge, where increased levels of urokinase plasminogen activator are found. PAI-1 could therefore serve to bridge cell surface with the ECM. We propose that the dual functions of PAI-1 (i.e., inhibition of urokinase activity and promotion of dynamic cell adhesion) may in part explain why incrased levels of PAI-1 in tumor is associated with enhanced tumor cell invasiviness.