Vitronectin

Vitronectin is a secreted glycoprotein found in blood plasma and in the extracellular matrix of numerous tissues. It is a high‑molecular‑weight protein that participates in cell adhesion, migration, and the regulation of proteolysis, and it can exist in multiple conformations and associations within the tissue environment.

A key feature of vitronectin is its RGD (arginine–glycine–aspartic acid) motif, which enables binding to several integrins, including αvβ3, αvβ5, and α5β1. Through these interactions, vitronectin promotes cell adhesion, spreading, and directed movement. It also binds to heparin/heparan sulfate proteoglycans, collagen, and laminin, and it can associate with the complex of plasminogen activator inhibitor‑1 (PAI‑1) and urokinase plasminogen activator (uPA), thereby modulating fibrinolysis and proteolytic activity in tissues.

Production and distribution: the liver is a major source of circulating vitronectin, but it is also synthesized by other cell types, including fibroblasts, endothelial cells, and adipocytes. In plasma, vitronectin circulates as a soluble protein, whereas in tissues it becomes part of the extracellular matrix and pericellular environments.

Functions and roles: beyond supporting cell adhesion and matrix remodeling, vitronectin participates in wound healing, regulation of coagulation and complement pathways, and angiogenesis. In cancer, VN signaling through integrins can influence tumor cell adhesion, motility, and invasion, contributing to the complexity of tumor–stroma interactions.

Clinical and research relevance: alterations in vitronectin levels and distribution have been observed in liver disease, inflammatory conditions, and certain cancers. Vitronectin is used as a substrate for in vitro cell culture and remains a focal point in studies of cell–ECM interactions and integrin signaling.