hspg-binding peptide corresponding to the exon 6a-encoded domain of vegf inhibits tumor growth by blocking angiogenesis in murine modelhspg-binding肽对应的外显子6 a-encoded领域vegf抑制肿瘤的生长通过阻断血管生成在小鼠模型中.pdfVIP

HSPG-Binding Peptide Corresponding to the Exon 6a-Encoded Domain of VEGF Inhibits Tumor Growth by Blocking Angiogenesis in Murine Model 1 1 1,2 Tong-Young Lee *, Judah Folkman , Kashi Javaherian * 1Vascular Biology Program, Department of Surgery, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America, 2 Center of Cancer Systems Biology, Department of Medicine, St. Elizabeth’s Medical Center, School of Medicine, Tufts University, Boston, Massachusetts, United States of America Abstract Vascular endothelial growth factor VEGF165 is a critical element for development of the vascular system in physiological and pathological angiogenesis. VEGF isoforms have different affinities for heparan sulphate proteoglycan (HSPG) as well as for VEGF receptors; HSPGs are important regulators in vascular development. Therefore, inhibition of interactions between VEGF and HSPGs may prevent angiogenesis. Here, we demonstrate that an HSPG-binding synthetic peptide, corresponding to exon 6a-encoded domain of VEGF gene, has anti-angiogenic property. This 20 amino acids synthetic peptide prevents VEGF165 binding to several different cell types, mouse embryonic sections and inhibits endothelial cell migration, despite its absence in VEGF165 sequence. Our in vivo anti-tumor studies show that the peptide inhibits tumor growth in both mouse Lewis-Lung Carcinoma and human Liposarcoma tumor-bearing animal models. This is the first evidence that a synthetic VEGF fragment corresponding to exon 6a has functional antagonism both in vitro and in vivo. We conclude that the above HPSG binding peptide (6a-P) is a potent inhibitor of angiogenesis-dependent diseases. Citation: Lee T-Y, Folkman J, Javaherian K (2010) HSPG-Binding Peptide Corresponding to