Identification of Tumor Specific Peptide as EpCAM Ligand and Its Potential Diagnostic and Therapeutic Clinical Application.
Xiaowen MaXiaoyu KangLei HeJiming ZhouJuan ZhouMatthew B SturmDavid G BeerRork KuickDerek J NancarrowHenry D AppelmanZhijun PangWeina LiCun ZhangWei ZhangYingqi ZhangThomas D WangMeng LiPublished in: Molecular pharmaceutics (2019)
Tumor targeting agents are being developed for early tumor detection and therapeutics. We previously identified the peptide SNFYMPL (SNF*) and demonstrated its specific binding to human esophageal specimens of high-grade dysplasia (HGD) and adenocarcinoma with imaging ex vivo. Here, we aim to identify the target for this peptide and investigate its potential applications in imaging and drug delivery. With SNF* conjugated affinity chromatography, mass spectrum, Western blot, enzyme-linked immunosorbent assay (ELISA), and molecular docking, we found that the epithelial cell adhesion molecule (EpCAM) was the potential target of SNF*. Next, we showed that FITC-labeled SNF* (SNF*-FITC) colocalized with EpCAM antibody on the surface of esophageal adenocarcinoma cells OE33, and SNF*-FITC binding patterns significantly changed after EpCAM knockdown or exogenous EpCAM transfection. With the data from TCGA, we demonstrated that EpCAM was overexpressed in 17 types of cancers. Using colon and gastric adenocarcinoma cells and tissues as examples, we found that SNF*-FITC bound in a pattern was colocalized with EpCAM antibody, and the SNF* binding did not upregulate the EpCAM downstream Wnt signals. Subsequently, we conjugated SNF* with our previously constructed poly(histidine)-PEG/DSPE copolymer micelles. SNF* labeling significantly improved the micelle binding with colon and gastric adenocarcinoma cells in vitro, and enhanced the antitumor effects and decreased the toxicities of the micelles in vivo. In conclusion, we identified and validated SNF* as a specific peptide for EpCAM. The future potential use of SNF* peptide in multiple tumor surveillance and tumor-targeted therapeutics was demonstrated.
Keyphrases
- cell adhesion
- circulating tumor cells
- drug delivery
- induced apoptosis
- molecular docking
- squamous cell carcinoma
- cancer therapy
- high grade
- cell cycle arrest
- high resolution
- stem cells
- public health
- endothelial cells
- cell proliferation
- cell death
- drug release
- high throughput
- oxidative stress
- locally advanced
- low grade
- wastewater treatment
- electronic health record
- single cell
- climate change
- young adults
- current status
- quantum dots
- human health
- ultrasound guided
- bioinformatics analysis
- childhood cancer