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

我们发现血小板因子4 （PF-4）阻断碱性成纤维细胞生长因子（bFGF）与其受体的结合，并抑制1型胶原凝胶（体外血管生成）中内皮细胞的自发管形成。这些生物活性定位于PF-4分子的羧基末端肝素结合域。由至少10个氨基酸组成的合成肽（KKIIKKLLES: C-10）的羧基端PF-4保持这些活性。为了用最少的氨基酸合成活性肽，我们合成了KKIIKK (C-6)，并将其活性与C-10进行了比较。我们在C-6中未观察到任何生物活性。因此，除了电荷外，肽的三维结构也可能是表达其活性的重要因素。最后，我们测试了C-10在小鼠体内接种肿瘤细胞后是否阻断血管生成的作用。C-10对肿瘤细胞诱导的血管生成无明显影响。这些结果表明，肿瘤血管生成可能涉及多种因素，仅消除bFGF的作用可能是不够的。

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.