title: Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation.
abstract: Basic fibroblast growth factor (bFGF) has been implicated in tumor growth via interactions with its receptors (FGFRs) on the cell surface and therefore, bFGF/FGFRs are considered essential targets for cancer therapy. Herein, a consensus heptapeptide (LSPPRYP) was identified for the first time from a phage display heptapeptide library after three sequential rounds of biopanning against FGFR-expressing cells with competitive displacement of phage by bFGF, followed by subtraction of non-specific binding by FGFR-deficient cells. Phage bearing LSPPRYP showed high levels of binding to Balb/c 3T3 cells expressing high-affinity bFGF-binding FGFR (bFGFR), but not to the cells that do not express bFGFR (Cos-7), or express a very low affinity bFGFR (HaCat). The selected-phage-derived peptide synthesized by solid phase method using a rapid and practical Fmoc strategy was found to specifically compete with bFGF for binding to its receptors, inhibit bFGF-stimulated cell proliferation by inducing cell cycle arrest, and block bFGF-induced activation of Erk1 and Erk2 kinase in B16-F10 melanoma cells. Importantly, treatment of melanoma-bearing mice with the synthetic peptide significantly suppressed tumor growth. The results demonstrate a strong anticancer activity of the isolated bFGFR-binding peptide (and its future derivatives), which may have great potential for cancer therapy.
authors.affiliation: School of Pharmaceutical Science, Key Laboratory of Biotechnology and Pharmaceutical Engineering of Zhejiang Province, Wenzhou Medical College, Wenzhou, PR China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wu
authors.forename: Huixian
authors.initials: H
authors.lastname: Huang
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.forename: Shaoqiang
authors.initials: S
authors.lastname: Lin
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Yan
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.forename: Jianzhang
authors.initials: J
authors.lastname: Wu
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D048708:Cell Growth Processes / Q000187:drug effects; D002522:Chlorocebus aethiops; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D011485:Protein Binding
chemical_list: D010455:Peptides; D016222:Fibroblast Growth Factor 2