Elucidation and clinical implication of breast cancer stem cells

Abstract

Current evidence supports “cancer stem cell hypothesis” that a small subpopulation composed of cancer stem cells (CSCs) in a tumor can have self-renewing ability and tumorigenesis, and generate tumor to recapitulate a heterogeneous population of cancer cells in hierarchical fashion. CSC hypothesis brings a paradigm shift for cancer biology and treatment strategies. In breast cancer, representative markers of CSCs have reported to be CD44+/CD24- and ALDH1, which enable us to isolate cancer cells with tumorigenesis and self-renewal. We have researched ribophorin II (RPN2) that is associated with drug resistance and stemness in breast cancer. RPN2 is one of oligosaccaryltransferase complex that is responsible for N-glycosylation of proteins. By controlling N-glycosylation of p-glycoprotein, RPN2 is causative of drug resistance in breast cancer patients receiving docetaxel. Furthermore, RPN2 is also controlling tumorigenesis and metastatic ability of breast CSCs with CD44+/CD24-. When RPN2 was suppressed in breast CSCs, CSCs lost both characteristics. We have also researched the mechanisms how to control breast CSCs by RPN2. Circulating tumor cells (CTCs) are crucial process to tumor metastasis that causes cancers to be incurable. In several cancers including breast cancer, CTCs were detected in patients with early and advanced diseases. Current researches revealed that CTC was an independent prognostic factor and a predictive marker in metastatic breast cancer. In addition, breast CTCs were reported to change HER2 status from primary breast cancer. Although their significance is not completely recognized, it is important to clarify molecular biology of CTCs and association between CTCs and CSCs. Here, we review the experimental and clinical evidence for the involvement of CSCs in breast cancer development, focusing on the common characteristics of CTCs.