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

Anal Chem. 2019 Jul 2;91(13):8374-8382. doi: 10.1021/acs.analchem.9b01181. Epub 2019 Jun 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms / blood
  • Breast Neoplasms / pathology*
  • Cell Proliferation
  • Cell Separation / methods*
  • Dendrimers / chemistry*
  • Epithelial Cell Adhesion Molecule / chemistry
  • Epithelial Cell Adhesion Molecule / metabolism
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Male
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / pathology*
  • Pilot Projects
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / pathology*
  • Transforming Growth Factor beta1 / administration & dosage*
  • Tumor Cells, Cultured

Substances

  • Dendrimers
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • TGFB1 protein, human
  • Transforming Growth Factor beta1