Epithelial-Mesenchymal Transitioned Tumor Cells Capture for Detecting Tumor Progression

作者：Satelli Arun; Mitra Abhisek; Brownlee Zachary; Xia Xueqing; Bellister Seth; Overman Michael J; Kopetz Scott; Ellis Lee M; Meng Qing H; Li Shulin^*

来源：Clinical Cancer Research, 2015, 21(4): 899-906.

DOI：10.1158/1078-0432.CCR-14-0894

Purpose: This study aimed to detect cell-surface vimentin (CSV) on the surface of epithelial-mesenchymal transitioned (EMT) circulating tumor cells (CTCs) from blood of patients with epithelial cancers.
Experimental Design: In this study, 101 patients undergoing post-surgery adjuvant chemotherapy for metastatic colon cancer were recruited. EMT CTCs were detected from blood of patients using 84-1 monoclonal antibody against CSV as a marker. EMT CTCs isolated were characterized further using EMT-specific markers, fluorescent in situ hybridization and single cell mutation analysis.
Results: Using 84-1 antibody, we detected CSV exclusively on EMT CTCs from a variety of tumor types but not in the surrounding normal cells in the blood. The antibody exhibited very high specificity and sensitivity towards different epithelial cancer cells. With this antibody, we detected and enumerated EMT CTCs from patients. From our observations, we defined a cutoff of < five or = five EMT CTCs as optimal threshold with respect to therapeutic response using ROC curves. Using this defined threshold, the presence of = five EMT CTCs was associated with progressive disease, while patients with less than five EMT CTCs showed therapeutic response.
Conclusion: Taken together, number of EMT CTCs detected correlated with the therapeutic outcome of the disease. These results establish cell-surface vimentin as a universal marker for EMT CTCs from a wide variety of tumor types and thus provide the foundation for emerging CTC detection technologies and for studying the molecular regulation of these EMT CTCs.

• 出版日期2015-2-15