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

Oncogene volume 29, pages 2672–2680 (2010)Cite this article

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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 × 103 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.

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Acknowledgements

This work was supported by Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A062598; NHC) and by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MEST) (No. 20090079165; CNH).

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Authors and Affiliations

  1. Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

    M-Q Gao

  2. Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea

    Y-P Choi, S Kang & N-H Cho

  3. Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea

    J H Youn

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  1. M-Q Gao
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Correspondence to N-H Cho.

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Gao, MQ., Choi, YP., Kang, S. et al. CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells. Oncogene 29, 2672–2680 (2010). https://doi.org/10.1038/onc.2010.35

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