Generation and degradation of human endostatin proteins by various proteinases

The angiogenesis inhibitor endostatin is a fragment of the NC1 domain of co llagen XVIII. The generation of endostatin has been investigated only in mu rine hemangioendothelioma cell cultures and was ascribed to cathepsin L. Di stinct endostatin-like fragments were detected in human tissues and serum. To identify proteinases able to generate such fragments, we incubated human NC1 with proteinases of all classes, including cathepsin L. Eleven out of 12 generate fragments with an N-terminus within the same 15 residue stretch as those occurring physiologically, indicating that this region is sensiti ve to many proteinases. None correspond to mouse endostatin. However, the e fficiencies of these proteinases differed markedly. Some proteinases also p roved to degrade endostatin, pointing to another regulatory loop of angioge nesis. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.