CD24+ ovary cancer cells exhibit an invasive mesenchymal phenotype

Abstract

We recently reported that the subset of CD24+ cells in ovarian cancer possesses various cancer stem cell properties. In this study, we further show that this subpopulation of ovarian cancer cells exhibits an epithelial–mesenchymal transition (EMT) phenotype, high invasive capacity, and CXCR4/SDF-1-mediated chemotactic migration. We evaluated CD24 expression in various ovarian cancer cell lines by flow cytometric analysis. CAOV3 and a primary ovarian cancer cell line Clone 4 were sorted into CD24+ and CD24− subpopulations by FACS and Western blot, cell invasion, adhesion, and in vitro chemotaxis assays were performed with these two subpopulations. We also assessed the effects of shRNA depletion of CD24 in CAOV3 and Clone 4 cells by Western blot and cell invasion assays. CD24 expression in ovarian cancer cell lines correlated with aggressive histologic subtypes of epithelial ovarian cancer. The CD24+ subpopulation was also more invasive than the CD24− subpopulation and showed higher CXCR4/SDF-1-mediated chemotactic migration. CD24+ cells exhibited an EMT phenotype as characterized by loss of E-cadherin expression and gain of vimentin, Twist, and Snail1 expression. In addition, CD24+ cells stimulated cell attachment to fibronectin through the activation of β1 integrin. Depletion of CD24 expression by CD24 shRNA efficiently suppressed cell invasion and induced downregulation of CXCR4 as well as loss of the EMT phenotype. In conclusion, CD24 expression in ovarian cancer may be related to tumor aggressiveness, in particular cell invasion and chemotactic migration. Therefore, CD24 may be a good candidate for a therapeutic target for ovarian cancer.