Isolation and characterization of cancer stem cells from a heterogeneous population in human ovarian cancer

Abstract

[한글]

[영문]Cancer stem cells (CSCs) have been identified in solid tumors and cancer cell lines. Here, we isolated a series of cancer cell clones, which were heterogeneous in growth rate, cell cycle distribution, and expression profile of genes and proteins, from ovarian tumor specimens of a patient and identified a subpopulation enriched for ovarian CSCs defined by CD24 phenotype. Experiments in vitro demonstrated CD24+ subpopulation possessed stem cell-like characteristics of remaining quiescence and more chemoresistance compared to CD24- fraction, as well as a specific capacity for self-renewal and differentiation. In addition, injection of 5×103 CD24+ cells was able to form tumor xenografts in nude mice, whereas equal number of CD24- cells remained nontumorigenic. We also found CD24+ cells expressed higher mRNA levels of some “stemness” genes, including Nestin, β-catenin, Bmi-1, Oct4, Oct3/4, Notch1, and Notch4 which were involved in modulating many functions of stem cells, and lower E-cadherin mRNA level than CD24- cells. Altogether, these observations suggest human ovarian tumor cells are organized as a hierarchy and CD24 demarcates an ovarian cancer-initiating cell population. These findings will have important clinical applications for developing effective therapeutic strategies to treat ovarian cancer.