Maspin, the molecular bridge between the plasminogen activator system and beta1 integrin that facilitates cell adhesion.

ABSTRACT

Maspin is a non-inhibitory serine protease inhibitor (serpin) that influences many cellular functions including adhesion, migration, and invasion. The underlying molecular mechanisms that facilitate these actions are still being elucidated. In this study we determined the mechanism by which maspin mediates increased MCF10A cell adhesion. Utilizing competition peptides and mutation analyses, we discovered two unique regions (amino acid residues 190-202 and 260-275) involved in facilitating the increased adhesion function of maspin. In addition, we demonstrate that the urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) complex is required for the localization and adhesion function of maspin. Finally, we showed that maspin, uPAR, and ß1 integrin co-immunoprecipitate, suggesting a novel maspin-uPA-uPAR-ß1 integrin mega-complex that regulates mammary epithelial cell adhesion.