Dendrimer-Based Platform for Effective Capture of Tumor Cells after TGFβ1-Induced Epithelial-Mesenchymal Transition

Ja Hye Myung, Ashley Cha, Kevin A. Tam, Michael Poellmann, Alain Borgeat, Roohollah Sharifi, Robert E. Molokie, Gina Votta-Velis, Seungpyo Hong

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Detection of circulating tumor cells (CTCs) relying on their expression of epithelial cell markers, such as epithelial cell adhesion molecule (EpCAM), has been commonly used. However, this approach unlikely captures CTCs that have undergone the process of epithelial-mesenchymal transition (EMT). In this study, we have induced EMT of in vitro prostate (PCa) and breast cancer (BCa) cell lines by treatment of transforming growth factor β 1 (TGFβ1), a pleiotropic cytokine with transition-regulating activities. We found that the TGFβ1-treated, post-EMT cells exhibited up to a 45% reduction in binding affinity to antibodies against EpCAM (aEpCAM). To overcome this limitation, we designed our capture platform that integrates a unique combination of biomimetic cell rolling, dendrimer-mediated multivalent binding, and antibody cocktails of aEpCAM/aEGFR/aHER-2. Our capture surfaces resulted in up to 98% capture efficiency of post-EMT cells from mixtures of TGFβ1-treated and untreated cancer cells spiked in culture media and human blood. In a clinical pilot study, our CTC device was also able to capture rare CTCs from PCa patients with significantly enhanced capture sensitivity and purity compared to the control surface with aEpCAM only, demonstrating its potential to provide a reliable detection solution for CTCs regardless of their EMT status.

Original languageEnglish
Pages (from-to)8374-8382
Number of pages9
JournalAnalytical Chemistry
Volume91
Issue number13
DOIs
Publication statusPublished - 2019 Jul 2

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry

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