Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage.

抄録

Cancer stem-like cell subpopulations, referred to as “side-population” SP cells have been identified in several tumors based on their ability to efflux the fluorescent dye Hoechst 33342. While SP cells have been identified in the normal human endometrium, they have not been characterized in endometrial cancer. In this study, we isolated and characterized the SP cells in an endometrial cancer cell line and in rat endometrial cells expressing oncogenic [¹²Val] human K-Ras protein. These SP cells showed 1) reductions in the expression levels of differentiation markers 2) long-term repopulating properties 3) self-renewal capacity 4) enhancement of migration and podia formation 5) enhancement of tumorigenicity 6) bipotent developmental potential (tumor cells and stroma-like cells). In nude mice, SP cells formed large, invasive tumors, which were composed of both tumor and extracellular matrix enriched stromal-like cells. The expression levels of vimentin,αsmooth muscle actin and collagen III were enhanced in SP-tumors compared with the levels in non-SP-tumors. Analysis of microdissected samples and fluorescence in situ hybridization showed that the stromal -like cells with enriched ECM contained human DNA, confirming that the stromal-like cells were derived from the inoculated cells. In a matrigel assay, SP cells differentiated into _-SMA -expressing cells. These findings demonstrate that SP cells have cancer stem like cell features including the potential to differentiate into the mesenchymal cell lineage.