CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells

Oncogene. 2010 May 6;29(18):2672-80. doi: 10.1038/onc.2010.35. Epub 2010 Mar 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / analysis
  • CD24 Antigen / analysis*
  • Female
  • Glycoproteins / analysis
  • Humans
  • Mice
  • Neoplastic Stem Cells / pathology*
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / pathology*
  • Peptides / analysis
  • Proto-Oncogene Proteins c-kit / analysis

Substances

  • AC133 Antigen
  • Antigens, CD
  • CD24 Antigen
  • Glycoproteins
  • Peptides
  • Proto-Oncogene Proteins c-kit