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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2013
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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. |
format | Online Article Text |
id | pubmed-3858566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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