Breast Cancer Stem Cells Transition between Epithelial and Mesenchymal States Reflective of their Normal Counterparts

TLDR

Breast cancer stem cells are implicated in metastasis, therapy resistance, and relapse, yet it remains unclear whether known markers identify distinct or overlapping cell populations. The study proposes that plasticity between EMT- and MET-like states enables BCSCs to invade, disseminate, and grow at metastatic sites. BCSCs exist in distinct mesenchymal-like (CD24⁻CD44⁺) and epithelial-like (ALDH⁺) states that differ in quiescence, localization, and proliferation, yet share similar gene‑expression profiles across breast cancer subtypes and resemble normal basal and luminal stem cells.

Abstract

Previous studies have suggested that breast cancer stem cells (BCSCs) mediate metastasis, are resistant to radiation and chemotherapy, and contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSCs. Here, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition [EMT]) and epithelial-like (mesenchymal-epithelial transition [MET]) states. Mesenchymal-like BCSCs characterized as CD24−CD44+ are primarily quiescent and localized at the tumor invasive front, whereas epithelial-like BCSCs express aldehyde dehydrogenase (ALDH), are proliferative, and are located more centrally. The gene-expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across different molecular subtypes of breast cancer, and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs that allows them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination, and growth at metastatic sites.