[A fragment of collagen XVIII inhibits angiogenesis].
BACKGROUND
Malignant tumours may produce substances with both stimulatory and inhibitory effect on angiogenesis.


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.


CONCLUSIONS
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.
Zätterström
U K
UK
Harvard Medical School, Department of Cell Biology, 240 Longwood Ave, Boston, MA 02115, USA.
Fukai
N
N
Olsen
B R
BR
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D003094:Collagen / Q000737:chemistry*; D016228:Endothelial Growth Factors / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D010446:Peptide Fragments; D003094:Collagen