A short peptide domain of platelet factor 4 blocks angiogenic key events induced by FGF-2

FASEB J. 2001 Mar;15(3):550-2. doi: 10.1096/fj.00-0285fje. Epub 2001 Jan 5.


Platelet factor 4 (PF-4) is a CXC-chemokine with strong anti-angiogenic properties. We have shown previously that PF-4 inhibits angiogenesis by associating directly with fibroblast growth factor 2 (FGF-2), inhibiting its dimerization, and blocking FGF-2 binding to endothelial cells. We now have characterized a small peptide domain (PF-447-70) derived from the C-terminus of PF-4, which conserves anti-angiogenic effects of the parent protein. PF-447-70 inhibited internalization of 125I-FGF-2 by endothelial cells in a time-dependent manner. The peptide reduced FGF-2-stimulated cell migration to control levels in wounded monolayers of bovine capillary endothelial cells. PF-447-70 also reduced FGF-2 induced phosphorylation of MAP kinases ERK-1 and ERK-2, which are essential for migration and survival of endothelial cells. In a serum-free ex vivo angiogenesis assay, the peptide blocked microvessel outgrowth by 89%. A single amino acid substitution within PF-447-70 abolished all inhibitory activities. To simulate a real anti-angiogenic treatment situation, we administered PF-447-70 systemically to mice implanted subcutaneously with FGF-2 containing gelatin sponges with the result of sparse, scattered, and immature vessel growth. The small peptide fragment derived from the angio-inhibitory CXC-chemokine PF-4 might be used as a starting point to develop anti-angiogenic designer drugs for angiogenesis-dependent pathologies such as cancer, diabetic retinopathy, and rheumatoid arthritis.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aorta
  • Cell Division
  • Cell Movement
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Culture Techniques
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Enzyme Activation
  • Fibroblast Growth Factor 2 / metabolism*
  • Humans
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Neovascularization, Physiologic / drug effects*
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology*
  • Platelet Factor 4 / chemistry*
  • Platelet Factor 4 / genetics
  • Platelet Factor 4 / pharmacology*
  • Protein Structure, Tertiary
  • Rats
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / metabolism


  • Culture Media, Serum-Free
  • Peptide Fragments
  • Receptors, Fibroblast Growth Factor
  • platelet factor 4 (47-70)
  • Fibroblast Growth Factor 2
  • Platelet Factor 4
  • FGFR2 protein, human
  • Fgfr2 protein, mouse
  • Fgfr2 protein, rat
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 2
  • Mitogen-Activated Protein Kinases