| First Author | Felbor U | Year | 2000 |
| Journal | EMBO J | Volume | 19 |
| Issue | 6 | Pages | 1187-94 |
| PubMed ID | 10716919 | Mgi Jnum | J:289459 |
| Mgi Id | MGI:6437015 | Doi | 10.1093/emboj/19.6.1187 |
| Citation | Felbor U, et al. (2000) Secreted cathepsin L generates endostatin from collagen XVIII. EMBO J 19(6):1187-94 |
| abstractText | 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. |
