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

MITSUHIRO NAKAMURA, XIUZHI ZHANG, YASUNARI MIZUMOTO, YOSHIKO MAIDA, YUKIKO BONO, MASAHIRO TAKAKURA, SATORU KYO
2013 International Journal of Oncology  
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 CD133cells, we noted several key factors involved in the aggressive behavior of cells, including ABCG2 and matrix
more » ... teinase (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 CD133cells. 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 CD133cells 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.
doi:10.3892/ijo.2013.2230 pmid:24366104 fatcat:x4zjieril5d4npx57wpwzlda7q