Related Experiment Video
Updated: Aug 30, 2026
Analysis of Cancer Cell Invasion and Anti-metastatic Drug Screening Using Hydrogel Micro-chamber Array (HMCA)-based Plates
Published on: October 25, 2018
Aminopeptidase inhibitor bestatin stimulates microvascular endothelial cell invasion in a fibrin matrix
Yvette van Hensbergen1, Henk J Broxterman, Erna Peters
1Department of Medical Oncology, Amsterdam, VU University Medical Center, The Netherlands.
Abstract:
The 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 micro M; the increase was 3.7-fold at 125 micro M; while high concentrations (>250 micro M), 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.
Insights
Bestatin, an aminopeptidase inhibitor, surprisingly promoted blood vessel formation in fibrin matrices, contrary to its known anti-angiogenic effects. This suggests other enzymes, not CD13, drive this pro-angiogenic activity in tumor stroma.
Area of Science:
- Biochemistry
- Cell Biology
- Angiogenesis Research
Background:
- Aminopeptidase inhibitor bestatin exhibits anti-angiogenic properties, primarily attributed to CD13 inhibition.
- Tumor angiogenesis often occurs within fibrin-rich stroma, a microenvironment not previously studied for bestatin's effects.
Purpose of the Study:
- To investigate the impact of bestatin on microvascular endothelial capillary-like tube formation within a fibrin matrix.
- To explore the role of CD13 and other aminopeptidases in bestatin-mediated angiogenesis in fibrin.
Main Methods:
- Assessing capillary-like tube formation by endothelial cells in fibrin gels with varying bestatin concentrations.
- Utilizing CD13-blocking antibodies (WM15, MY-7) and other aminopeptidase inhibitors (amastatin, actinonin).
- Evaluating the involvement of the urokinase plasminogen activator/urokinase plasminogen activator receptor (u-PA/u-PAR) system.
Main Results:
- Bestatin demonstrated a dose-dependent enhancement of capillary-like tube formation, with significant effects observed at 8 µM and a 3.7-fold increase at 125 µM.
- High bestatin concentrations (>250 µM) induced matrix degradation, consistent with anti-angiogenic effects seen in other systems.
- CD13-blocking antibodies and other inhibitors showed a trend towards enhanced tube formation, but results were not statistically significant.
Conclusions:
- Bestatin promotes angiogenesis in a fibrin matrix, a novel pro-angiogenic effect distinct from its CD13-inhibiting properties.
- Aminopeptidases other than CD13 likely mediate bestatin's pro-angiogenic activity in fibrin.
- These findings are crucial for understanding bestatin's therapeutic potential as an anti-tumor agent.
More Related Videos
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
Some...
01:24Regulation of Angiogenesis and Blood Supply
01:35Cancer Cell Migration through Invadopodia