Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers

Andrew J. Armstrong, Matthew S. Marengo, Sebastian Oltean, Gabor Kemeny, Rhonda L. Bitting, James D. Turnbull, Christina I. Herold, Paul K. Marcom, Daniel J. George, Mariano A. Garcia-Blanco

Research output: Contribution to journalArticlepeer-review

532 Scopus citations

Abstract

During cancer progression, malignant cells undergo epithelial-mesenchymal transitions (EMT) and mesenchymal- epithelial transitions (MET) as part of a broad invasion and metastasis program. We previously observed MET events among lung metastases in a preclinical model of prostate adenocarcinoma that suggested a relationship between epithelial plasticity and metastatic spread. We thus sought to translate these findings into clinical evidence by examining the existence ofEMTin circulating tumor cells (CTC) from patients with progressive metastatic solid tumors, with a focus on men with castration-resistant prostate cancer (CRPC) and women with metastatic breast cancer. We showed that the majority (>80%) of these CTCs in patients with metastatic CRPC coexpress epithelial proteins such as epithelial cell adhesion molecule (EpCAM), cytokeratins (CK), and E-cadherin, with mesenchymal proteins including vimentin, N-cadherin and O-cadherin, and the stem cell marker CD133. Equally, we found that more than 75% of CTCs from women with metastatic breast cancer coexpress CK, vimentin, and N-cadherin. The existence and high frequency of these CTCs coexpressing epithelial, mesenchymal, and stem cell markers in patients with progressive metastases has important implications for the application and interpretation of approved methods to detect CTCs.

Original languageEnglish (US)
Pages (from-to)997-1007
Number of pages11
JournalMolecular Cancer Research
Volume9
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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