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Aminopeptidase inhibitor bestatin stimulates microvascular endothelial cell invasion in a fibrin matrix
- Source :
- Thrombosis and Haemostasis, 90(5), 921-9. Schattauer GmbH, Thrombosis and Haemostasis, 5, 90, 921-929, van Hensbergen, Y, Broxterman, H J, Peters, E, Rana, S, Elderkamp, YW, van Hinsbergh, V W M & Koolwijk, P 2003, ' Aminopeptidase inhibitor bestatin stimulates microvascular endothelial cell invasion in a fibrin matrix. ', Thrombosis and Haemostasis, vol. 90, no. 5, pp. 921-9 . https://doi.org/10.1160/TH03-03-0144
- Publication Year :
- 2003
-
Abstract
- SummaryThe aminopeptidase inhibitor bestatin has been shown to have anti-angiogenic effects in a number of model systems. These effects are thought to result from inhibition of CD13 activity. Because tumor angiogenesis can evolve in a fibrin-rich stroma matrix we have studied for the first time the effects of bestatin on microvascular endothelial capillary-like tube formation in a fibrin matrix. Bestatin enhanced the formation of capillary-like tubes dose-dependently. Its effects were apparent at 8 µM; the increase was 3.7-fold at 125 µM; while high concentrations (>250 µM), that were shown to have anti-angiogenic effects in other systems, caused extensive matrix degradation. Specific CD13-blocking antibodies WM15 and MY-7, and the aminopeptidase inhibitors amastatin and actinonin also enhanced capillary-like tube formation (maximally 1.5-fold), but these effects did not reach statistical significance. The effect of bestatin was not due to a change in uPAR availability because the relative involvement of the u-PA/u-PAR activity was not altered by bestatin. In view of the present findings we hypothesize that aminopeptidases other than CD13 predominantly contribute to the observed pro-angiogenic effect of bestatin in a fibrin matrix. The identification of this novel effect of bestatin is important in the light of the proposed use of bestatin as anti-angiogenic and/or anti-tumor agent.
- Subjects :
- Integrins
Umbilical Veins
Biomedical Research
Angiogenesis
Bestatin
urokinase
Aminopeptidase
Aminopeptidases
amastatin
chemistry.chemical_compound
angiogenesis
Cell Movement
antibody
dose response
endothelium cell
Actinonin
antineoplastic agent
Cells, Cultured
Tube formation
actinonin
WM15 antibody
drug effect
Hematology
cell invasion
Cell biology
unclassified drug
enzyme activity
Endothelial stem cell
Vascular endothelial growth factor A
Biochemistry
priority journal
u-PAR
Urinary Plasminogen Activator
hypothesis
vascular endothelium
tumor
enzyme inhibitor
Antigens, CD13
Neovascularization, Physiologic
Ubenimex
Receptors, Cell Surface
Biology
CD13 Antigens
Receptors, Urokinase Plasminogen Activator
Amastatin
Leucine
urokinase receptor
stroma
Humans
controlled study
protein expression
microsomal aminopeptidase
Fibrin
concentration (parameters)
Dose-Response Relationship, Drug
MY 7 antibody
vasculotropin
human cell
Microcirculation
basic fibroblast growth factor
Urokinase-Type Plasminogen Activator
chemistry
Endothelium, Vascular
Subjects
Details
- Language :
- English
- ISSN :
- 03406245
- Volume :
- 90
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Thrombosis and Haemostasis
- Accession number :
- edsair.doi.dedup.....2a4127b12d41774a1ae027ce7a5571b7