Suppression of tumor growth and metastasis by a VEGFR-1 antagonizing peptide identified from a phage display library
✍ Scribed by Ping An; Hetian Lei; Jianzhi Zhang; Shumei Song; Luowen He; Genglin Jin; Xiaoying Liu; Jian Wu; Lin Meng; Meisheng Liu; Chengchao Shou
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- French
- Weight
- 360 KB
- Volume
- 111
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Although the VEGF‐Flk‐1‐pathway has been known as the major driving force of angiogenesis, new evidence has shown that VEGFR‐1/Flt‐1 plays important roles during the neovascularization under pathological conditions including tumor, atherosclerosis and arthritis. In search of Flt‐1 receptor antagonizing peptides, we screened a phage display 12‐mer‐peptide library with recombinant Flt‐1 protein. Seven candidate peptides were identified that specifically bound to VEGF receptor Flt‐1, of which peptide F56 (WHSDMEWWYLLG) almost abolished VEGF binding to receptor Flt‐1 in vitro. In vivo, F56 fused with DHFR (DHFR‐F56) inhibited angiogenesis in a CAM assay. Moreover, DHFR‐F56 significantly inhibited the growth of nodules of human gastric cancer cell line MGC‐803 in BALB/c nude mice. Histological analyses showed that necrosis of the implanted tumor was markedly enhanced following treatment with DHFR‐F56. In the severe combined immunodeficiency disease (SCID) mouse model for studying metastasis of the human breast cancer cell line BICR‐H1, synthetic peptide F56 significantly inhibited tumor growth and lung metastases. Taken together, our results have demonstrated that peptide F56, as a Flt‐1 receptor antagonist, fulfilled the antiangiogenic and antimetastatic effects by specifically interfering with the interaction between VEGF and receptor Flt‐1. Thus, short peptide F56 may have clinical potential in tumor therapy. © 2004 Wiley‐Liss, Inc.