Vitronectin in Vascular Context: Facets of a Multitalented Matricellular Protein

Vitronectin is an abundant adhesive glycoprotein in blood plasma and is found associated with different extracellular matrix sites, the vessel wall, and tumor cells, particularly upon tissue remodeling, injury/repair, or under disease conditions. Plasma vitronectin is a structurally labile molecule that may be converted into a multimeric/multivalent form by interaction with various (hemostatic) factors or through surface binding. Several distinct binding domains along the vitronectin sequence for integrin-type cell adhesion receptors, for urokinase receptor or proteoglycans as well as for growth factors, endow vascular matrix- or fibrin-associated vitronectin with differentiated cell attachment and aggregatory properties. These were found to be relevant for modulation of the cell matrix interface in angiogenesis, hemostasis and thrombus formation, or wound repair, respectively. Other vitronectin ligands include plasminogen activator inhibitor (PAI)-1 or high molecular weight kininogen that confer strong antiadhesive functions upon integrin- or urokinase receptor-mediated cell interactions with vitronectin. Together, vitronectin acts as a potent matricellular factor, coordinating cell migration with pericellular proteolysis and growth factor signaling at sites of tissue remodeling or in tumors. Structure-function studies of such vitronectin-related ligands and receptors lead to the characterization of their mode of action, also stimulating the search for new antagonists in tumor angiogenesis, platelet aggregation, or atherosclerosis. This review focuses on new developments in vitronectin biology, with particular emphasis on regulatory mechanisms of the protein in the context of cell adhesion/migration/proliferation and cell-dependent proteolysis, relevant for our understanding of hemostasis, thrombosis, tissue repair, and vascular diseases.