Abstract
We have studied the role of plasminogen activator inhibitor-1 (PA1-1) in cell migration. The migration of human amnion WISH cells and human epidermoid carcinoma HEp-2 cells was inhibited by active, but not latent or reactive centre-cleaved PAI-1, both in an assay measuring migration from microcarrier beads and in a modified Boyden-chamber assay. The PAI-1 effect was independent of inhibition of plasminogen activators as a reactivecentre PAI-1 mutant inhibited migration as effectively as wild-type PAI-1. Cell migration in our assays was inhibited by a cyclic RGD-peptide and monoclonal antibodies to VN and to VN-binding integrins. PAI-1 specifically interferred with VN- and VN-binding integrin-dependent cell migration as it inhibited migration onto VN-coated surfaces, but not onto FN-coated surfaces In in vitro binding assays, active, but not latent or rective centrecleaved PAI-1 inhibited integrin binding to VN. Five different monoclonal antibodies against the urokinase receptor (uPAR) were found to have no effect on migration from beads while two antibodies inhibited migration in the Boyden-chamber assay In conclusion, it appears that PAI-1 inhibits cell migration by competing for integrin binding to VN, while the interference of PAI-1 with uPAR/VN interaction may play a secondary role. As the PAI-1 effects was independent of plasminogen activator inhibition, the data define a new serpin effect unrelated to inhibition of proteinases, with PAI-1 being able to regulate eel! migration over vitronectin-rich extracellular matrix sites.
| Original language | English |
|---|---|
| Pages (from-to) | 11 |
| Number of pages | 1 |
| Journal | Fibrinolysis and Proteolysis |
| Volume | 11 |
| Issue number | SUPPL. 3 |
| State | Published - 1997 |
| Externally published | Yes |