The BioGRID | PUBLICATION VIEW

	EMBO J. Mar (2000); 19(6):1187-94
Secreted cathepsin L generates endostatin from collagen XVIII.
Felbor U, Dreier L, Bryant RA, Ploegh HL, Olsen BR, Mothes W
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Abstract: Endostatin, an inhibitor of angiogenesis and tumor growth, was identified originally in conditioned media of murine hemangioendothelioma (EOMA) cells. N-terminal amino acid sequencing demonstrated that it corresponds to a fragment of basement membrane collagen XVIII. Here we report that cathepsin L is secreted by EOMA cells and is responsible for the generation of endostatin with the predicted N-terminus, while metalloproteases produce larger fragments in a parallel processing pathway. Efficient endostatin generation requires a moderately acidic pH similar to the pericellular milieu of tumors. The secretion of cathepsin L by a tumor cell line of endothelial origin suggests that this cathepsin may play a role in angiogenesis. We propose that cleavage within collagen XVIII's protease-sensitive region evolved to regulate excessive proteolysis in conditions of induced angiogenesis.
[PUBMED: 10716919]