title: Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers.
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 of EMT in 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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. andrew.armstrong@duke.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Marengo
authors.forename: Sebastian
authors.initials: S
authors.lastname: Oltean
authors.forename: Gabor
authors.initials: G
authors.lastname: Kemeny
authors.forename: Rhonda L
authors.initials: RL
authors.lastname: Bitting
authors.forename: James D
authors.initials: JD
authors.lastname: Turnbull
authors.forename: Christina I
authors.initials: CI
authors.lastname: Herold
authors.forename: Paul K
authors.initials: PK
authors.lastname: Marcom
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Mariano A
authors.initials: MA
authors.lastname: Garcia-Blanco
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor