Selection of Aptamers Against Vimentin for Isolation and Release of Circulating Tumor Cells Undergoing Epithelial Mesenchymal Transition

摘要

Circulating tumor cells (CTCs) undergoing epithelial mesenchymal transition (EMT) play an essential role in metastasis and have a better correlation with poor disease outcomes, but the most current affinity-based enrichment methods rely on targeting epithelial markers, which are less effective in capturing CTCs undergoing EMT. Herein, we identified and optimized an aptamer (ZYSC) sequence with high binding affinity and specificity against cell surface vimentin (CSV), which is overexpressed on the post-EMT CTCs. Not only can the hairpin-structured ZYSC aptamer specifically recognize a number of cancer cells with native CSV expression, but it can also bind to CSV expressed on EMT-cells. The K-d value of the ZYSC aptamer against CSV-positive T24 cells was found to be 38 +/- 4 nM. Using the evolved ZYSC aptamer and multivalent ZYSC aptamer-functionalized chip, we were able to isolate CTCs from the blood of adenocarcinoma, sarcoma, and carcinosarcoma patients. Overall, this ZYSC aptamer and isolation method bring a fresh approach to CTCs analysis, which not only detects CTCs from nonepithelial origin, but also provides an efficient way to in-depth study the role of post-EMT CTCs in clinical application and metastasis mechanisms.