Circulating Tumor Cells from Patients with Advanced Prostate and Breast Cancer Display Both Epithelial and Mesenchymal Markers

TLDR

During cancer progression, malignant cells undergo epithelial‑mesenchymal and mesenchymal‑epithelial transitions as part of a broad invasion and metastasis program. The study aimed to translate preclinical evidence of MET into clinical data by investigating EMT in circulating tumor cells from patients with progressive metastatic solid tumors, focusing on castration‑resistant prostate cancer and metastatic breast cancer. Researchers examined circulating tumor cells for EMT markers in these patient cohorts, assessing the expression of epithelial, mesenchymal, and stem cell proteins. They found that over 80 % of CTCs in metastatic CRPC and more than 75 % in metastatic breast cancer coexpress epithelial, mesenchymal, and stem cell markers, highlighting the prevalence of hybrid phenotypes and the need to reassess current CTC detection methods.

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.