[A fragment of collagen XVIII inhibits angiogenesis].

BACKGROUND: Malignant tumours may produce substances with both stimulatory and inhibitory effect on angiogenesis. MATERIAL AND METHODS: A protein fragment with angiogenesis-inhibiting potential was recently identified in conditioned media from a murine endothelial tumour cell line. RESULTS: The angiogenesis inhibitor, endostatin, is a 20 kDa C-terminal fragment of collagen XVIII, a proteoglycan/collagen found in vessel walls and basement membranes. The generation of endostatin or endostatin-like collagen XVIII fragments is catalyzed by proteolytic enzymes, including cathepsin L and matrix metalloproteases, that cleave peptide bonds within the protease-sensitive hinge region of the C-terminal domain. INTERPRETATION: The physiological processing of collagen XVIII to endostatin may represent a local control mechanism for the regulation of angiogenesis. The outcome of ongoing clinical trials will determine the role of endostatin as a possible angiogenesis-inhibiting drug in the future.