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.
Molecular Mechanisms of Angiogenesis Laboratory (INSERM E0113), Université Bordeaux I, Avenue des Facultés, 33 405 Talence, France. a.bikfalvi@angio.u-bordeaux1.fr
Andreas
A
Bikfalvi
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