Secreted cathepsin L generates endostatin from collagen XVIII
Secreted cathepsin L generates endostatin from collagen XVIII
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DOI：
10.1093/emboj/19.6.1187
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发表时间：
2000-03-15
期刊：
影响因子：
11.4
通讯作者：
Mothes, W
中科院分区：
文献类型：
--
作者：
Felbor, U;Dreier, L;Mothes, W
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.
