Angiostatin: An endogenous inhibitor of angiogenesis and tumor growth

Angiogenesis is an important process of new microblood vessel formation under both physiological and pathological conditions and is likely regulated by a balance between angiogenic stimulators and inhibitors. Given the dependence of tumor growth and metastasis on angiogenesis, endogenous angiogenesis inhibitors are important for suppression of tumor progression. Angiostatin is a major endogenous angiogenesis inhibitor having the ability to regress tumor in various animal models. Although the mechanism of angiostatin formation in vivo, as well as the molecular mechanism of angiostatin action, remains elusive, in vitro studies have suggested that this protein is generated from plasminogen by multiple enzymatic actions. In this review, we describe the current understanding of the responsible proteinases for angiostatin generation and of the mechanism of angiostatin action.