The development of new modes of diagnosis and targeted
therapy for
lung cancer is dependent on the identification of unique cell surface features on
cancer cells and isolation of
reagents that bind with high affinity and specificity to these
biomarkers. We recently isolated a 20-mer
peptide which binds to the
lung adenocarcinoma cell line, H2009, from a phage-displayed
peptide library. We show here that the cellular receptor for this
peptide, TP H2009.1, is the uniquely expressed
integrin, alphavbeta6, and the
peptide binding to
lung cancer cell lines correlates to
integrin expression. The
peptide is able to mediate cell-specific uptake of a fluorescent nanoparticle via this receptor. Expression of alphavbeta6 was assessed on 311 human
lung cancer samples. The expression of this
integrin is widespread in early-stage nonsmall cell lung
carcinoma (NSCLC). Log-rank test and Cox regression analyses show that expression of this
integrin is significantly associated with poor patient outcome. Preferential expression is observed in the
tumors compared with the surrounding normal lung tissue. Our data indicate that alphavbeta6 is a prognostic
biomarker for NSCLC and may serve as a receptor for targeted
therapies. Thus, cell-specific
peptides isolated from phage biopanning can be used for the discovery of cell surface
biomarkers, emphasizing the utility of
peptide libraries to probe the surface of a cell.