MicroRNA expression analysis of mammospheres cultured from human breast cancers.

PURPOSE: There is accumulating evidence suggests that tumors are initiated and maintained by a small fraction of tumor-initiating cells (TICs). TICs can be enriched by mammospheres culturing without surface markers. MicroRNAs participated in many important processes of life including regulating tumorigenicity of TICs. However, roles of miRNAs in TICs of breast cancer are still unknown.

METHODS: We compared mammospheres formation of four breast cancer cell lines, cultured mammospheres from breast cancers specimens of three patients and compared microRNAs profiling of mammospheres cultured from breast cancer specimens with differentiated progenies.

RESULTS: Three of the four breast cancer cell lines showed the ability of mammospheres formation. The proportions of CD24(-)cells in mammospheres were increased significantly in the three cell lines. The expression of genes associated with stem cells and chemoresistance increased significantly after mammospheres formation. Breast cancer cells isolated from patients' specimens survived in nonadherent culture conditions generated mammospheres with ability of self-renewal and bilineage potential. MicroRNA expression profiling of mammospheres compared with differentiated progenies isolated and propagated from the three patients identified 17 microRNAs. And the target genes of these miRNAs are involved in several key signaling pathways.

CONCLUSIONS: The results suggested that mammospheres were enriched in TICs and proved a valuable model for studies of breast cancer TICs in vitro, microRNAs played critical roles in maintenance of stemness properties of mammospheres and provided novel insights into breast cancer therapy.