Recent developments in the inhibition of angiogenesis: examples from studies on platelet factor-4 and the VEGF/VEGFR system.
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.
Bikfalvi
Andreas
A
Molecular Mechanisms of Angiogenesis Laboratory (INSERM E0113), Université Bordeaux I, Avenue des Facultés, 33 405 Talence, France. a.bikfalvi@angio.u-bordeaux1.fr
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D016228:Endothelial Growth Factors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D010456:Peptides, Cyclic / Q000494:pharmacology; D010978:Platelet Factor 4 / Q000737:chemistry / Q000494:pharmacology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D042442:Vascular Endothelial Growth Factors / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D010456:Peptides, Cyclic; D042442:Vascular Endothelial Growth Factors; C478485:cyclo-VEGI; D010978:Platelet Factor 4; D040262:Receptors, Vascular Endothelial Growth Factor