Recent developments in the inhibition of angiogenesis: examples from studies on platelet factor-4 and the VEGF/VEGFR system.

Abstract

Inhibition of angiogenesis is an important strategy to block tumor growth and invasion. We discuss herein results from our ongoing investigations on platelet factor-4 (PF-4) and the VEGF/VEGFR system. Platelet factor-4 (PF-4) is an anti-angiogenic ELR-negative chemokine. PF-4 inhibits endothelial cell proliferation and migration, and angiogenesis in vitro and in vivo. We have studied the structure and anti-angiogenic activities of a C-terminal fragment of PF-4 named PF-4 CTF. This molecule retains anti-angiogenic activity, blocks the interaction of angiogenesis factors with their receptors and may also be improved by mutation or domain-swapping. It seems, therefore, to be a good candidate for further development. Furthermore, we have developed a cyclic vascular endothelial growth inhibitor (Cyclo VEGI) from the structure of VEGF-A. In aqueous solution, cyclo-VEGI adopts an alpha helix conformation. Cyclo-VEGI inhibits binding of iodinated VEGF(165) to endothelial cells and angiogenesis. Furthermore, cyclo-VEGI significantly blocks the growth of established intracranial glioma in nude and syngeneic mice and improves survival.

• Authors: Andreas Bikfalvi
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 68 Issue 6 Pg. 1017-21 (Sep 15 2004) ISSN: 0006-2952 [Print] England
• PMID: 15313395 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Angiogenesis Inhibitors
• Endothelial Growth Factors
• Peptides, Cyclic
• Vascular Endothelial Growth Factors
• cyclo-VEGI
• Platelet Factor 4
• Receptors, Vascular Endothelial Growth Factor

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Endothelial Growth Factors (pharmacology)
• Humans
• Mice
• Peptides, Cyclic (pharmacology)
• Platelet Factor 4 (chemistry, pharmacology)
• Receptors, Vascular Endothelial Growth Factor (antagonists & inhibitors)
• Vascular Endothelial Growth Factors (pharmacology)