Screening a phage display library for a novel FGF8b-binding peptide with anti-tumor effect on prostate cancer

Journal Article · Wed May 01 04:00:00 EDT 2013 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2013.02.007· OSTI ID:22278236

Wang, Wenhui; Chen, Xilei; Li, Tao; Li, Yanmei; Wang, Ruixue; He, Dan; Luo, Wu ^[1]; Li, Xiaokun ^[1]; Wu, Xiaoping ^[1]

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1. Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632 (China)

Fibroblast growth factor 8b (FGF8b) is the major isoform of FGF8 expressed in prostate cancer and it correlates with the stage and grade of the disease. FGF8b has been considered as a potential target for prostate cancer therapy. Here we isolated 12 specific FGF8b-binding phage clones by screening a phage display heptapeptide library with FGF8b. The peptide (HSQAAVP, named as P12) corresponding to one of these clones showed high homology to the immunoglobulin-like (Ig-like) domain II(D2) of high-affinity FGF8b receptor (FGFR3c), contained 3 identical amino acids (AVP) to the authentic FGFR3 D2 sequence aa 163–169 (LLAVPAA) directly participating in ligand binding, carried the same charges as its corresponding motif (aa163–169) in FGFR3c, suggesting that P12 may have a greater potential to interrupt FGF8b binding to its receptors than other identified heptapeptides do. Functional analysis indicated that synthetic P12 peptides mediate significant inhibition of FGF8b-induced cell proliferation, arrest cell cycle at the G0/G1 phase via suppression of Cyclin D1 and PCNA, and blockade of the activations of Erk1/2 and Akt cascades in both prostate cancer cells and vascular endothelial cells. The results demonstrated that the P12 peptide acting as an FGF8b antagonist may have therapeutic potential in prostate cancer. - Highlights: ► A novel FGF8b-binding peptide P12 was isolated from a phage display library. ► The mechanisms for P12 peptide inhibiting cell proliferation were proposed. ► P12 caused cell cycle arrest at G0/G1 phase via suppression of Cyclin D1 and PCNA. ► P12 suppressed FGF8b-induced activations of Akt and MAP kinases. ► P12 acting as an FGF8b antagonist may have therapeutic potential in prostate cancer.

• OSTI ID: 22278236
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 8 Vol. 319; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
BACTERIOPHAGES
CELL CYCLE
FIBROBLASTS
GROWTH FACTORS
IMMUNOGLOBULINS
NEOPLASMS
PEPTIDES
PHOSPHOTRANSFERASES
PROSTATE
RECEPTORS