Stem cells in human breast cancer.

Increasing data support cancer as a stem cell-based disease. Cancer stem cells (CSCs) have been found in different human cancers, and recent evidence indicates that breast cancer originates from and is maintained by its own CSCs, as well as the normal mammary gland. Mammary stem cells and breast CSCs have been identified and purified in in vitro culture systems, transplantation assays and/or by cell surface antigen identification. Cell surface markers enable the functional isolation of stem cells that can initiate and propagate tumorigenesis in mammary gland. These observations have dramatic biological and clinical significance due to increasing evidence suggesting that the recurrence of human cancer and treatment failure may reflect the intrinsic quiescence and drug resistance of CSCs. Thus, the CSC hypothesis provides fundamental implications for understanding breast carcinogenesis and for developing new strategies for breast cancer prevention and therapy for advanced disease. Further strategies to isolate breast CSCs, to find additional trustworthy surface markers, and to compare gene expression pathways profiles with their normal stem cells counterparts are necessary to more accurately define putative breast cell-lineage markers for the different cell types present in the mature mammary gland and to identify potential therapeutical targets in breast cancer. This review discusses the current knowledge about stem cells and CSCs, focusing on mammary stem cells and breast CSCs, and their consequences for breast tumorigenesis and implications for breast cancer susceptibility, prognosis, and treatment.