Breast Cancer Stem Cell Heterogeneity, Plasticity and Treatment Strategies

Breast cancer stem cells (BCSCs) are a small proportion of stem-like breast cancer cells with more tumorigenic and metastatic capacity in comparison to the bulk tumor cells, which are capable of self-renewal and generating differentiated cells. BCSCs are resistant to chemotherapy and radiotherapy. More and more research indicate that BCSCs are heterogeneous and have plasticity, which refer to their ability to switch between different subtypes of stem-like cells and differentiated cells. There is some evidence showing that BCSC heterogeneity and plasticity plays a role on therapeutic resistance and metastasis of breast cancer. In this review, we discussed the roles of extrinsic (rewired tumor microenvironment, including hypoxia, microbiota) and intrinsic (pro-tumor signaling) factors on regulating BCSC heterogeneity and plasticity, leading to various malignant behaviors of BCSCs, including epithelial-mesenchymal transition (EMT)/mesenchymal-epithelial transition (MET), immune evasion, vasculogenesis and so on. Moreover, we also discussed the potential therapeutic strategies to target BCSCs.