A peptide selected by biopanning identifies the integrin alphavbeta6 as a prognostic biomarker for nonsmall cell lung cancer.
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.
Elayadi
Anissa N
AN
Division of Translational Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Samli
Kausar N
KN
Prudkin
Ludmila
L
Liu
Ying-Horng
YH
Bian
Aihua
A
Xie
Xian-Jin
XJ
Wistuba
Ignacio I
II
Roth
Jack A
JA
McGuire
Michael J
MJ
Brown
Kathlynn C
KC
D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism*; D011379:Prognosis; D046888:Tissue Array Analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D016023:Integrins; D019151:Peptide Library; D010455:Peptides; C073878:integrin alphavbeta6