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Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
Published on: September 30, 2019
A novel melanoma-targeting peptide screened by phage display exhibits antitumor activity
Alisson L Matsuo1, Aparecida S Tanaka, Maria A Juliano
1Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, Rua Botucatu 862, oitavo andar, São Paulo, São Paulo 04023-062, Brazil. almatsuo@unifesp.br
Abstract:
Peptide display on the phage surface has been widely used to identify specific peptides targeting several in vivo and in vitro tumor cells and the tumor vasculature, playing a role in the discovery of bioactive antitumor agents. Bioactive peptides have been selected to target important tumor receptors or apoptosis-associated molecules such as p53. Presently, we attempted to identify potentially antitumor bioactive molecules using the whole cell surface as the recognizable static matrix. Such methodology could be advantageous in cancer therapy because it does not require previous characterization of target molecules. Using a C7C phage display library, we screened for peptides binding to the B16F10-Nex2 melanoma cell surface after pre-absorption on melan-A lineage. After a few rounds of enrichment, 50 phages were randomly selected, amplified, and tested for inhibition of tumor cell proliferation. Seven were active, and the corresponding peptide of each phage was chemically synthesized in the cyclic form and tested in vitro. Three peptides were able to preferentially inhibit the melanoma lineage. A unique peptide, [-CSSRTMHHC-], exhibited in vivo antitumor inhibitory activity against a subcutaneous melanoma challenge, rendering 60% of mice without tumor growth. Further, this peptide also markedly inhibited in vitro and in vivo the tumor cell invasion and cell-to-cell adhesiveness in vitro. This is the first report on a bioactive peptide derived from a C7C library active against whole melanoma cells in vitro and in vivo.
Insights
Researchers discovered a novel peptide that effectively inhibits melanoma tumor growth and spread. This peptide, identified using phage display technology, shows significant potential as a new cancer therapy agent.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Phage display is a powerful tool for identifying peptides targeting specific cells.
- Previous studies focused on known tumor receptors or molecules.
- A novel approach using whole cell surfaces as targets could bypass the need for target characterization.
Purpose of the Study:
- To identify novel bioactive peptides with antitumor activity using a whole cell surface display method.
- To evaluate the efficacy of identified peptides against melanoma cells in vitro and in vivo.
- To explore the potential of these peptides in cancer therapy.
Main Methods:
- Utilized a C7C phage display library to screen for peptides binding to B16F10-Nex2 melanoma cells.
- Enriched and selected phages displaying peptides with anti-melanoma activity.
- Synthesized and tested active peptides for inhibition of tumor cell proliferation, invasion, and adhesion.
Main Results:
- Identified seven active peptides, with three preferentially inhibiting melanoma cell growth.
- A unique cyclic peptide, [-CSSRTMHHC-], demonstrated significant in vivo antitumor activity, preventing tumor growth in 60% of mice.
- This peptide also inhibited melanoma cell invasion and cell-to-cell adhesion in vitro and in vivo.
Conclusions:
- A novel bioactive peptide derived from a C7C phage display library has been identified.
- This peptide exhibits potent in vitro and in vivo anti-melanoma activity, targeting whole melanoma cells.
- The findings represent a significant advancement in the discovery of novel anti-cancer agents and therapeutic strategies.
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