Tetranectin Binds to the Kringle 1-4 Form of Angiostatin and Modifies Its Functional Activity

Tetranectin is a plasminogen kringle 4 domain-binding protein present in plasma and various tissue locations. Decreased plasma tetranectin or increased tetranectin in stroma of cancers correlates with cancer progression and adverse prognosis. A possible mechanism through which tetranectin could influence cancer progression is by altering activities of plasminogen or the plasminogen fragment, angiostatin. Tetranectin was found to bind to the kringle 1-4 form of angiostatin (AST $;{\text{K1-4}}$ ). In addition, tetranectin inhibited binding of plasminogen or AST $;{\text{K1-4}}$ to extracellular matrix (ECM) deposited by endothelial cells. Finally, tetranectin partially counteracted the ability of AST $;{\text{K1-4}}$ to inhibit proliferation of endothelial cells. This latter effect of tetranectin was specific for AST $;{\text{K1-4}}$ since it did not counteract the antiproliferative activities of the kringle 1-3 form of angiostatin (AST $;{\text{K1-3}}$ ) or endostatin. These findings suggest that tetranectin may modulate angiogenesis through interactions with AST.