Landscape Phage Probes for Breast Cancer Cell Receptors
O.A. Fagbohun, D. Bedi, P.K. Jayanna, P.A. Deinnocentes, R.C. Bird, V.A. Petrenko
Auburn University, US
Keywords: landscape phage, breast cancer, receptor
Abstract:Identifying overexpressed receptors on cancer cells using phage probes is a promising approach for improvement of cancer diagnosis, targeted drug and gene therapy. As a step towards this goal, two landscape phage libraries f8/8 and f8/9, with 8- and 9-mer with guest peptides on the pVIII major coat, were used to select phage probes interacting with breast cancer cells MCF-7 and ZR-75-1. Specificity and selectivity of the phage probes was confirmed by testing them in phage capture assay with target cancer cells and unrelated MCF-10A cells (normal breast epithelia), HepG2 cells (human hepatocellular carcinoma) and serum; an unrelated phage displaying the peptide VPEGAFSS was the negative control. Phage probes displaying the peptides VEEGGYIAA and VTLLEPGE were the most selective for MCF-7 cells and ZR-75-1 cells respectively. Peptide sequences displayed on all the phage probes were analyzed for their similarities with primary and tertiary structures of ligands of overexpressed breast cancer cell receptors. Phage displaying peptides, VEEGGYIAA and VTLLEPGE show linear alignment similarities with EGF, whereas phage probes with peptides DVYSLAYPD and GHSLPPDM showed highest conformational alignment similarities with EGF. This emphasizes the vast potential of landscape phage probes in cell surface mapping of linear and conformational ligand-receptor interacting surfaces.