PMID- 10626789
OWN - NLM
STAT- MEDLINE
DCOM- 20000124
LR  - 20071114
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 24
DP  - 1999 Dec 15
TI  - The generation of endostatin is mediated by elastase.
PG  - 6052-6
AB  - Endostatin, a potent inhibitor of angiogenesis and tumor growth, is a
      COOH-terminal fragment of collagen XVIII derived through cleavage of an Ala-His
      linkage by an as yet unidentified endostatin-processing enzyme. Endostatin was
      originally isolated from the conditioned medium of hemangioendothelioma (EOMA)
      cells. By investigating the processing of collagen XVIII to endostatin by EOMA
      cells, we show here that the generation of endostatin can be mediated by an
      elastase activity. We also show that several members of the elastase family can
      act as an endostatin-processing enzyme by specifically cleaving the Ala-His
      linkage and releasing endostatin from a precursor molecule. We further suggest
      that the generation of endostatin from collagen XVIII is at least a two-step
      process, involving a metal-dependent early step and an elastase
      activity-dependent final step.
FAU - Wen, W
AU  - Wen W
AD  - Department of Surgery, The Children's Hospital, Boston, Massachusetts 02115, USA.
FAU - Moses, M A
AU  - Moses MA
FAU - Wiederschain, D
AU  - Wiederschain D
FAU - Arbiser, J L
AU  - Arbiser JL
FAU - Folkman, J
AU  - Folkman J
LA  - eng
GR  - KO8 AR 02096-01/AR/NIAMS NIH HHS/United States
GR  - R01 CA64481/CA/NCI NIH HHS/United States
GR  - R03 AR 44947-03/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Collagen Type XVIII)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Endostatins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Peptide Fragments)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.21.36 (Pancreatic Elastase)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Collagen/*biosynthesis/*metabolism/pharmacology
MH  - Collagen Type XVIII
MH  - Culture Media, Conditioned
MH  - Endostatins
MH  - Enzyme Inhibitors/pharmacology
MH  - Hemangioendothelioma/enzymology/*metabolism
MH  - Humans
MH  - Metalloendopeptidases/antagonists & inhibitors
MH  - Neovascularization, Pathologic
MH  - Pancreatic Elastase/antagonists & inhibitors/*metabolism
MH  - Peptide Fragments/*biosynthesis/pharmacology
MH  - Peptide Hydrolases/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2000/01/08 00:00
MHDA- 2000/01/08 00:01
CRDT- 2000/01/08 00:00
PHST- 2000/01/08 00:00 [pubmed]
PHST- 2000/01/08 00:01 [medline]
PHST- 2000/01/08 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Dec 15;59(24):6052-6.