title: CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells.
abstract: Cancer stem cells (CSCs) have been identified in solid tumors and cancer cell lines. In this study, 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 sub-population enriched for ovarian CSCs defined by CD24 phenotype. Experiments in vitro demonstrated CD24(+) sub-population possessed stem cell-like characteristics of remaining quiescence and more chemoresistant compared with CD24(-) fraction, as well as a specific capacity for self-renewal and differentiation. In addition, injection of 5 x 10(3) CD24(+) cells was able to form tumor xenografts in nude mice, whereas equal number of CD24(-) cells remained nontumorigenic. We also found that CD24(+) cells expressed higher mRNA levels of some 'stemness' genes, including Nestin, beta-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.
authors.affiliation: Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: M-Q
authors.initials: MQ
authors.lastname: Gao
authors.forename: Y-P
authors.initials: YP
authors.lastname: Choi
authors.forename: S
authors.initials: S
authors.lastname: Kang
authors.forename: J H
authors.initials: JH
authors.lastname: Youn
authors.forename: N-H
authors.initials: NH
authors.lastname: Cho
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D051927:CD24 Antigen / Q000032:analysis*; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000473:pathology*; D010455:Peptides / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D051927:CD24 Antigen; D006023:Glycoproteins; D010455:Peptides; D019009:Proto-Oncogene Proteins c-kit