Targeting aggressive prostate cancer-associated CD44v6 using phage display selected peptides
Autor: | Susan L. Deutscher, Ying Peng, Austin R. Prater |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Phage display Peptide 03 medical and health sciences Prostate cancer 0302 clinical medicine Cancer stem cell medicine chemistry.chemical_classification Tissue microarray biology CD44 CD44v6 prostate cancer medicine.disease Phenotype peptide 3. Good health 030104 developmental biology Oncology chemistry Cell culture 030220 oncology & carcinogenesis biology.protein Cancer research biomarker phage display Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | There is a crucial need to identify new biomarkers associated with aggressive prostate cancer (PCa) including those associated with cancer stem cells (CSCs). CD44v6, generated by alternative splicing of CD44, has been proposed as a CSC biomarker due to its correlation with aggressive PCa disease. We hypothesized that phage display selected peptides that target CD44v6 may serve as theranostic agents for aggressive PCa. Here, a 15 amino acid peptide ("PFT") was identified by affinity selection against a peptide derived from the v6 region of CD44v6. Synthesized PFT exhibited specific binding to CD44v6 with an equilibrium dissociation constant (Kd) of 743.4 nM. PFT also bound CD44v6 highly expressed on human PCa cell lines. Further, an aggressive form of PCa cells (v6A3) was isolated and tagged by a novel CSC reporter vector. The v6A3 cells had a CSC-like phenotype including enriched CD44v6 expression, enhanced clonogenicity, resistance to chemotherapeutics, and generation of heterogeneous offspring. PFT exhibited preferential binding to v6A3 cells compared to parental cells. Immunohistofluorescence studies with human PCa tissue microarrays (TMA) indicated that PFT was highly accurate in detecting CD44v6-positive aggressive PCa cells, and staining positivity was significantly higher in late stage, metastatic and higher-grade samples. Taken together, this study provides for the first time phage display selected peptides that target CD44v6 overexpressed on PCa cells. Peptide PFT may be explored as an aid in the diagnosis and therapy of advanced PCa disease. |
Databáze: | OpenAIRE |
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