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Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library

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Targeting aggressive prostate cancer-associated CD44v6 using phage display selected peptides.

Ying Peng^1,2, Austin R Prater^1,2, Susan L Deutscher^1,2

¹Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA.

|November 22, 2017

Summary

This summary is machine-generated.

Researchers identified a peptide targeting CD44v6, a biomarker for aggressive prostate cancer (PCa) and cancer stem cells (CSCs). This peptide, PFT, shows promise for diagnosing and treating advanced PCa.

Keywords:

CD44v6 biomarker peptide phage display prostate cancer

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Area of Science:

Oncology
Biotechnology
Molecular Biology

Background:

Aggressive prostate cancer (PCa) requires novel biomarkers, particularly those linked to cancer stem cells (CSCs).
CD44v6, an alternative splice variant of CD44, is implicated as a CSC biomarker correlating with advanced PCa.
Targeting CD44v6 presents a potential strategy for developing theranostic agents for aggressive PCa.

Purpose of the Study:

To identify and characterize phage display selected peptides targeting CD44v6 for potential theranostic applications in aggressive PCa.
To evaluate the binding affinity and specificity of the identified peptide (PFT) to CD44v6.
To assess the potential of PFT as a diagnostic and therapeutic agent for advanced PCa.

Main Methods:

Phage display selection was employed to identify peptides binding to a CD44v6-derived peptide.
The synthesized peptide (PFT) was characterized for binding affinity (Kd) to CD44v6 using biochemical assays.
Human PCa cell lines, including a novel CSC-like variant (v6A3) with enriched CD44v6, were used for binding studies.
Immunohistofluorescence on PCa tissue microarrays (TMA) was performed to assess PFT's diagnostic accuracy in clinical samples.

Main Results:

A 15-amino acid peptide, PFT, was identified with specific binding to CD44v6 (Kd = 743.4 nM).
PFT demonstrated preferential binding to CD44v6-overexpressing aggressive PCa cells (v6A3) compared to parental cells.
Immunohistofluorescence studies confirmed PFT's high accuracy in detecting CD44v6-positive aggressive PCa cells, with increased positivity in late-stage, metastatic, and high-grade tumors.

Conclusions:

Phage display successfully identified peptides, including PFT, that specifically target CD44v6 overexpressed on PCa cells.
Peptide PFT exhibits potential as a theranostic agent for advanced prostate cancer, aiding in diagnosis and therapy.
This study highlights CD44v6 as a valuable target for developing novel strategies against aggressive PCa.