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Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation

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...

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Autores principales: Wu, Xiaoping, Huang, Huixian, Wang, Cong, Lin, Shaoqiang, Huang, Yadong, Wang, Yi, Liang, Guang, Yan, Qiuxia, Xiao, Jian, Wu, Jianzhang, Yang, Yongguang, Li, Xiaokun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858566/
https://www.ncbi.nlm.nih.gov/pubmed/24142482
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author Wu, Xiaoping
Huang, Huixian
Wang, Cong
Lin, Shaoqiang
Huang, Yadong
Wang, Yi
Liang, Guang
Yan, Qiuxia
Xiao, Jian
Wu, Jianzhang
Yang, Yongguang
Li, Xiaokun
author_facet Wu, Xiaoping
Huang, Huixian
Wang, Cong
Lin, Shaoqiang
Huang, Yadong
Wang, Yi
Liang, Guang
Yan, Qiuxia
Xiao, Jian
Wu, Jianzhang
Yang, Yongguang
Li, Xiaokun
author_sort Wu, Xiaoping
collection PubMed
description 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.
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spelling pubmed-38585662013-12-11 Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation Wu, Xiaoping Huang, Huixian Wang, Cong Lin, Shaoqiang Huang, Yadong Wang, Yi Liang, Guang Yan, Qiuxia Xiao, Jian Wu, Jianzhang Yang, Yongguang Li, Xiaokun Oncotarget Research Paper 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. Impact Journals LLC 2013-10-01 /pmc/articles/PMC3858566/ /pubmed/24142482 Text en Copyright: © 2013 Wu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Research Paper
Wu, Xiaoping
Huang, Huixian
Wang, Cong
Lin, Shaoqiang
Huang, Yadong
Wang, Yi
Liang, Guang
Yan, Qiuxia
Xiao, Jian
Wu, Jianzhang
Yang, Yongguang
Li, Xiaokun
Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation
title Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation
title_full Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation
title_fullStr Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation
title_full_unstemmed Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation
title_short Identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation
title_sort identification of a novel peptide that blocks basic fibroblast growth factor-mediated cell proliferation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858566/
https://www.ncbi.nlm.nih.gov/pubmed/24142482
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