EMT-independent detection of circulating tumor cells in human blood samples and pre-clinical mouse models of metastasis

Clin Exp Metastasis. 2021 Feb;38(1):97-108. doi: 10.1007/s10585-020-10070-y. Epub 2021 Jan 7.

Abstract

Circulating tumor cells (CTCs) present an opportunity to detect/monitor metastasis throughout disease progression. The CellSearch® is currently the only FDA-approved technology for CTC detection in patients. The main limitation of this system is its reliance on epithelial markers for CTC isolation/enumeration, which reduces its ability to detect more aggressive mesenchymal CTCs that are generated during metastasis via epithelial-to-mesenchymal transition (EMT). This Technical Note describes and validates two EMT-independent CTC analysis protocols; one for human samples using Parsortix® and one for mouse samples using VyCap. Parsortix® identifies significantly more mesenchymal human CTCs compared to the clinical CellSearch® test, and VyCap identifies significantly more CTCs compared to our mouse CellSearch® protocol regardless of EMT status. Recovery and downstream molecular characterization of CTCs is highly feasible using both Parsortix® and VyCap. The described CTC protocols can be used by investigators to study CTC generation, EMT and metastasis in both pre-clinical models and clinical samples.

Keywords: CellSearch®; Circulating tumor cells; Epithelial-to-mesenchymal transition; Metastasis; Parsortix®; VyCap.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms / blood*
  • Breast Neoplasms / pathology*
  • Cell Proliferation
  • Disease Progression
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / pathology*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays