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

• Published in: Oncogene Vol. 29; no. 18; pp. 2672 - 2680
• Main Authors: Gao, M-Q, Choi, Y-P, Kang, S, Youn, J H, Cho, N-H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.05.2010; Nature Publishing Group
• Subjects: 631/67/1059; 631/67/71; 692/699/67/1517/1709; AC133 Antigen; Animals; Antigens, CD - analysis; Apoptosis; Biological and medical sciences; Bmi protein; CD24 Antigen - analysis; Cell Biology; Cell cycle; Cell physiology; Cell self-renewal; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cloning; E-cadherin; Female; Female genital diseases; Fundamental and applied biological sciences. Psychology; Gene expression; Genetics; Glycoproteins - analysis; Growth rate; Gynecology. Andrology. Obstetrics; Human Genetics; Humans; Internal Medicine; Medical sciences; Medicine; Medicine & Public Health; Mice; Molecular and cellular biology; mRNA; Neoplastic Stem Cells - pathology; Nestin; Notch1 protein; Oct-4 protein; Oncology; original-article; Ovarian cancer; Ovarian Neoplasms - chemistry; Ovarian Neoplasms - pathology; Peptides - analysis; Phenotypes; Proto-Oncogene Proteins c-kit - analysis; Solid tumors; Stem cell transplantation; Stem cells; Tumor cell lines; Tumor cells; Tumors; Xenografts; β-Catenin; tumorigenicity; cancer stem cell; CD24; ovarian cancer; Ovarian diseases; Ovary cancer; Stem cell; Tumorigenicity; Malignant tumor; Carcinogenesis; Cancer; Female genital diseases
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2010.35

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 × 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, 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.