Inhibition of the binding of basic fibroblast growth factor to its receptor and angiogenesis by synthetic peptides related to platelet factor 4

1993 Fiscal Year Final Research Report Summary

• Project/Area Number: 03670629
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: KYUSHU UNIVERSITY ; OITA MEDICAL UNIVERSITY
• Principal Investigator: SATO Yasufumi Oita Medical University, First Department of Internal Medicine, Research Associate, 医学部, 助手 (50178779)
• Project Period (FY): 1991 – 1993
• Keywords: platelet factor 4(PF-4) / basic fibroblast growth factor(BFGF) / angiogenesis / heparin binding / synthetic peptide

Research Abstract

We have found that platelet factor 4 (PF-4) blocks the binding of basic fibroblast growth factor (bFGF) to its receptor and inhibits the spontaneous tube formation of endothelial cells in type 1 collagen gel (in vitro angiogenesis). These biological activities localize at the carboxyl-terminal heparin binding domain of the PF-4 molecule. A synthetic peptide composed with at least 10 amino acids (KKIIKKLLES : C-10) of carboxyl terminal PF-4 retains these activities. It is speculated that the cluster of basic amino acids, lysine, plays an important role, In order to obtain an active synthetic peptide with minimal amino acids, we composed KKIIKK (C-6) and compared its activities with that of C-10. We could not observe any biological activities in C-6. Therefore, not only electric charges but also three-dimensional structure of the peptide might be important to express its activity. Finally, we tested the in vivo effect of C-10 whether or not it blocked angiogenesis after the inoculation of tumor cells in mice. C-10 had no significant effect on angiogenesis induced by tumor cells. These results indicates that multiple factors may be involved in tumor angiogenesis, and the elimination of the effect of bFGF may not be sufficient.