Molecular characterization of CD133+ cancer stem-like cells in endometrial cancer

A small subset of cells with CD133 expression is thought to have increased chemoresistance and tumorigenicity, features of cancer stem cells (CSCs); the molecular mechanisms by which these properties arise remain unclear. We characterized CD133(+) endometrial cancer cells based on microarray analyses of Ishikawa cells. Of the genes upregulated in CD133(+) cells compared with CD133(-) cells, we noted several key factors involved in the aggressive behavior of cells, including ABCG2 and matrix metalloproteinase (MMP). Flow cytometric analyses identified a side-cell population (SP) with CSC features in Ishikawa cells, and they were found to be more enriched in CD133(+) cells than CD133(-) cells. In particular, CD133(+)/SP cells exhibited higher proliferative and colony-forming activity than CD133(+)/non-SP cells. Matrigel invasion assay revealed that CD133(+) cells have enhanced invasive capacity with elevated MT1-MMP expression. siRNA-based knockdown of MT1-MMP largely abolished the invasive capacity of CD133(+) cells, but not CD133(-) cells due to low levels of constitutive MT1-MMP1 expression. These findings demonstrate that increased chemoresistance and tumorigenic potential of CD133(+) cells are at least partly attributed to an enriched SP fraction as well as increased MMP-1 expression. These results will be of assistance in the establishment of molecular target therapy to CSCs in endometrial cancer.