[HTML][HTML] Secreted cathepsin L generates endostatin from collagen XVIII
U Felbor, L Dreier, RAR Bryant, HL Ploegh… - The EMBO …, 2000 - embopress.org
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 …
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 …
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.
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