Oncotarget

Research Papers:

Identification and validation of FGFR2 peptide for detection of early Barrett’s neoplasia

Juan Zhou, Lei He, Zhijun Pang, Henry D. Appelman, Rork Kuick, David G. Beer, Meng Li _ and Thomas D. Wang

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Oncotarget. 2017; 8:87095-87106. https://doi.org/10.18632/oncotarget.19764

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Abstract

Juan Zhou1, Lei He2, Zhijun Pang2, Henry D. Appelman3, Rork Kuick4, David G. Beer5, Meng Li2 and Thomas D. Wang1,6,7

1Department of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan 48109, USA

2Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi’an 710032, China

3Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA

4Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA

5Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA

6Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA

7Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA

Correspondence to:

Meng Li, email: [email protected]

Thomas D. Wang, email: [email protected]

Keywords: FGFR2, peptide, esophagus, cancer

Received: May 26, 2017     Accepted: July 03, 2017     Published: August 01, 2017

ABSTRACT

The incidence of esophageal adenocarcinoma (EAC) is rising rapidly, and early detection within the precursor state of Barrett’s esophagus (BE) is challenged by flat premalignant lesions that are difficult detect with conventional endoscopic surveillance. Overexpression of cell surface fibroblast growth factor receptor 2 (FGFR2) is an early event in progression of BE to EAC, and is a promising imaging target. We used phage display to identify the peptide SRRPASFRTARE that binds specifically to the extracellular domain of FGFR2. We labeled this peptide with a near-infrared fluorophore Cy5.5, and validated the specific binding to FGFR2 overexpressed in cells in vitro. We found high affinity kd = 68 nM and rapid binding k = 0.16 min-1 (6.2 min). In human esophageal specimens, we found significantly greater peptide binding to high-grade dysplasia (HGD) versus either BE or normal squamous epithelium, and good correlation with anti-FGFR2 antibody. We also observed significantly greater peptide binding to excised specimens of esophageal squamous cell carcinoma and gastric cancer compared to normal mucosa. These results demonstrate potential for this FGFR2 peptide to be used as a clinical imaging agent to guide tissue biopsy and improve methods for early detection of EAC and potentially other epithelial-derived cancers.


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