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Identification of cancer stem cell-like cells from human epithelial ovarian carcinoma cell line

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Abstract

Cancer stem cells (CSCs) play an important role in the development, invasion, and drug resistance of carcinoma, but the exact phenotype and characteristics of ovarian CSCs are still disputable. In this study, we identified cancer stem cell-like cells (CSC-LCs) and investigated their characteristics from the ovarian adenocarcinoma cell line 3AO. Our results showed that CSC-LCs were enriched in sphere-forming test and highly expressed CD44+CD24−. The spheres and CD24− cells possessed strong tumorigenic ability by transplantation into nonobese diabetic/severe combined immunodeficient mice. CD44+CD24− cells expressed stem cell markers and differentiated to CD44+CD24+ cells by immunofluorescence assay and fluorescence-activated cell-sorting analysis. In vitro experiments verified that CD44+CD24− cells were markedly resistant to carboplatin and paclitaxol. In conclusion, our study identifies the CD44+CD24− phenotype, self-renewal, high tumorigenicity, differentiation potential, and drug resistance of ovarian CSC-LCs. Our findings may provide the evidence needed to explore a new strategy in the treatment of ovarian cancer.

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References

  1. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM (2006) Cancer stem cells—perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res 66:9339–9344

    Article  CAS  PubMed  Google Scholar 

  2. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737

    Article  CAS  PubMed  Google Scholar 

  3. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988

    Article  CAS  PubMed  Google Scholar 

  4. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401

    Article  CAS  PubMed  Google Scholar 

  5. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951

    Article  CAS  PubMed  Google Scholar 

  6. Dalerba P, Cho RW, Clarke MF (2007) Cancer stem cells: models and concepts. Annu Rev Med 58:267–284

    Article  CAS  PubMed  Google Scholar 

  7. Olempska M, Eisenach PA, Ammerpohl O, Ungefroren H, Fandrich F, Kalthoff H (2007) Detection of tumor stem cell markers in pancreatic carcinoma cell lines. Hepatobiliary Pancreat Dis Int 6:92–97

    CAS  PubMed  Google Scholar 

  8. Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68:4311–4320

    Article  CAS  PubMed  Google Scholar 

  9. Fong MY, Kakar SS (2010) The role of cancer stem cells and the side population in epithelial ovarian cancer. Histol Histopathol 25:113–120

    CAS  PubMed  Google Scholar 

  10. Jordan CT, Guzman ML, Noble M (2006) Cancer stem cells. N Engl J Med 355:1253–1261

    Article  CAS  PubMed  Google Scholar 

  11. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111

    Article  CAS  PubMed  Google Scholar 

  12. Mimeault M, Hauke R, Mehta PP, Batra SK (2007) Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers. J Cell Mol Med 11:981–1011

    Article  CAS  PubMed  Google Scholar 

  13. Croker AK, Allan AL (2008) Cancer stem cells: implications for the progression and treatment of metastatic disease. J Cell Mol Med 12:374–390

    Article  CAS  PubMed  Google Scholar 

  14. Nossov V, Amneus M, Su F, Lang J, Janco JM, Reddy ST, Farias-Eisner R (2008) The early detection of ovarian cancer: from traditional methods to proteomics. Can we really do better than serum CA-125? Am J Obstet Gynecol 199:215–223

    Article  CAS  PubMed  Google Scholar 

  15. Bapat SA, Mali AM, Koppikar CB, Kurrey NK (2005) Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res 65:3025–3029

    CAS  PubMed  Google Scholar 

  16. Baba T, Convery PA, Matsumura N, Whitaker RS, Kondoh E, Perry T, Huang Z, Bentley RC, Mori S, Fujii S, Marks JR, Berchuck A, Murphy SK (2009) Epigenetic regulation of CD133 and tumorigenicity of CD133 + ovarian cancer cells. Oncogene 28:209–218

    Article  CAS  PubMed  Google Scholar 

  17. Tang DG, Patrawala L, Calhoun T, Bhatia B, Choy G, Schneider-Broussard R, Jeter C (2007) Prostate cancer stem/progenitor cells: identification, characterization, and implications. Mol Carcinog 46:1–14

    Article  CAS  PubMed  Google Scholar 

  18. Chambers I, Smith A (2004) Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23:7150–7160

    Article  CAS  PubMed  Google Scholar 

  19. Locke M, Heywood M, Fawell S, Mackenzie IC (2005) Retention of intrinsic stem cell hierarchies in carcinoma-derived cell lines. Cancer Res 65:8944–8950

    Article  CAS  PubMed  Google Scholar 

  20. Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65:9328–9337

    Article  CAS  PubMed  Google Scholar 

  21. Bunting KD (2002) ABC transporters as phenotypic markers and functional regulators of stem cells. Stem Cells 20:11–20

    Article  CAS  PubMed  Google Scholar 

  22. Mizrak D, Brittan M, Alison MR (2008) CD133: molecule of the moment. J Pathol 214:3–9

    Article  CAS  PubMed  Google Scholar 

  23. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828

    CAS  PubMed  Google Scholar 

  24. Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H (2006) Characterization of CD133 + hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun 351:820–824

    Article  CAS  PubMed  Google Scholar 

  25. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–1037

    Article  CAS  PubMed  Google Scholar 

  26. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111–115

    Article  CAS  PubMed  Google Scholar 

  27. Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, Conticello C, Ruco L, Peschle C, De Maria R (2008) Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 15:504–514

    Article  CAS  PubMed  Google Scholar 

  28. Ferrandina G, Bonanno G, Pierelli L, Perillo A, Procoli A, Mariotti A, Corallo M, Martinelli E, Rutella S, Paglia A, Zannoni G, Mancuso S, Scambia G (2008) Expression of CD133–1 and CD133–2 in ovarian cancer. Int J Gynecol Cancer 18:506–514

    Article  CAS  PubMed  Google Scholar 

  29. Inoue M, Kyo S, Fujita M, Enomoto T, Kondoh G (1994) Coexpression of the c-kit receptor and the stem cell factor in gynecological tumors. Cancer Res 54:3049–3053

    CAS  PubMed  Google Scholar 

  30. Tonary AM, Macdonald EA, Faught W, Senterman MK, Vanderhyden BC (2000) Lack of expression of c-KIT in ovarian cancers is associated with poor prognosis. Int J Cancer 89:242–250

    Article  CAS  PubMed  Google Scholar 

  31. Shaw TJ, Keszthelyi EJ, Tonary AM, Cada M, Vanderhyden BC (2002) Cyclic AMP in ovarian cancer cells both inhibits proliferation and increases c-KIT expression. Exp Cell Res 273:95–106

    Article  CAS  PubMed  Google Scholar 

  32. Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK, Trosko JE (2005) Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 26:495–502

    Article  CAS  PubMed  Google Scholar 

  33. Kondo T (2006) Brain cancer stem-like cells. Eur J Cancer 42:1237–1242

    Article  CAS  PubMed  Google Scholar 

  34. Ponti D, Zaffaroni N, Capelli C, Daidone MG (2006) Breast cancer stem cells: an overview. Eur J Cancer 42:1219–1224

    Article  CAS  PubMed  Google Scholar 

  35. Soltysova A, Altanerova V, Altaner C (2005) Cancer stem cells. Neoplasma 52:435–440

    CAS  PubMed  Google Scholar 

  36. Min C, Eddy SF, Sherr DH, Sonenshein GE (2008) NF-kappaB and epithelial to mesenchymal transition of cancer. J Cell Biochem 104:733–744

    Article  CAS  PubMed  Google Scholar 

  37. Kong D, Wang Z, Sarkar SH, Li Y, Banerjee S, Saliganan A, Kim HR, Cher ML, Sarkar FH (2008) Platelet-derived growth factor-D overexpression contributes to epithelial-mesenchymal transition of PC3 prostate cancer cells. Stem Cells 26:1425–1435

    Article  CAS  PubMed  Google Scholar 

  38. Larue L, Bellacosa A (2005) Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3’ kinase/AKT pathways. Oncogene 24:7443–7454

    Article  CAS  PubMed  Google Scholar 

  39. Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454

    Article  CAS  PubMed  Google Scholar 

  40. Kang Y, Massague J (2004) Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 118:277–279

    Article  CAS  PubMed  Google Scholar 

  41. Yoshida J, Horiuchi A, Kikuchi N, Hayashi A, Osada R, Ohira S, Shiozawa T, Konishi I (2009) Changes in the expression of E-cadherin repressors, Snail, Slug, SIP1, and Twist, in the development and progression of ovarian carcinoma: the important role of Snail in ovarian tumorigenesis and progression. Med Mol Morphol 42:82–91

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by the National Natural Science Foundation of China (Grant No. 30672230), the National Program on Key Basic Research Project of China (Grant No. 2009CB521800), and the Foundation of Health Department of Zhejiang Province of China (Grant No. 2007A129). We thank Professor Li ZT (Cancer Hospital of Fudan University), Mrs. Zhou J (Shanghai Cancer Institute, Shanghai Jiao Tong University), Mrs. Xu HL (Shanghai Cancer Institute, Shanghai Jiao Tong University), and Mr. Geng Q (Shanghai Cancer Institute, Shanghai Jiao Tong University), for technical assistance.

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Authors and Affiliations

  1. Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Women’s Reproductive Health Laboratory of Zhejiang Province, Zhejiang University, 2 Xueshi Road, Hangzhou, Zhejiang, China

    M. F. Shi, J. Jiao, W. G. Lu, F. Ye & X. Xie

  2. Shanghai Cancer Institute, Shanghai Jiao Tong University, 2200 Xietu Road, Shanghai, China

    Q. G. Dong

  3. Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    D. Ma

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  1. M. F. Shi
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  2. J. Jiao
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  3. W. G. Lu
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  4. F. Ye
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  5. D. Ma
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  6. Q. G. Dong
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Correspondence to Q. G. Dong or X. Xie.

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Shi, M.F., Jiao, J., Lu, W.G. et al. Identification of cancer stem cell-like cells from human epithelial ovarian carcinoma cell line. Cell. Mol. Life Sci. 67, 3915–3925 (2010). https://doi.org/10.1007/s00018-010-0420-9

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  • DOI: https://doi.org/10.1007/s00018-010-0420-9

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