Secreted cathepsin L generates endostatin from collagen XVIII

被引:375
|
作者
Felbor, U [1 ]
Dreier, L
Bryant, RAR
Ploegh, HL
Olsen, BR
Mothes, W
机构
[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Microbiol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Dent Med, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA
来源
EMBO JOURNAL | 2000年 / 19卷 / 06期
关键词
cathepsin L; collagen XVIII; endostatin; LHVS; metalloproteases;
D O I
10.1093/emboj/19.6.1187
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1187 / 1194
页数:8
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