Proteomics Using Mammospheres as a Model System to Identify Proteins Deregulated in Breast Cancer Stem Cells

Breast cancer stem cells (BCSC) exist within many types of breast cancers, functioning to initiate tumorigenesis and augment its progression. The protein profile associated with BCSC has yet to be extensively studied. Mammospheres have been widely employed as a model system to study BCSC. We used proteomics on the MCF-7 breast cancer cell line to compare protein expression in mammosphere-derived cells to that of parental monolayer cells. We identified 34 differentially expressed proteins, seven of which were overexpressed, with the remaining downregulated in mammosphere-derived cells. These differentially expressed proteins include those involved in cell metabolism such as GAPDH and fatty acid synthase, stress response proteins like Hsp27 and FKBP4, and signal transduction related proteins like GIPC1. The expression of breast cancer tumorigenesis and progression-promoting proteins GAPDH and FKBP4 were validated through western blotting. These two proteins are especially recognized for their role in breast cancer resistance to current chemotherapies. The data generated by mammosphere proteomics suggest that this system can identify novel targets for breast cancer stem cells and may provide insights into novel therapy of breast cancer.