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Effect of CD133 overexpression on the epithelial-to-mesenchymal transition in oral cancer cell lines

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Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world. In OSCC, CD133 promotes tumor invasion and metastasis by inducing the epithelial-to-mesenchymal transition (EMT). A small subset of cancer cells known as cancer stem cells (CSCs) are thought to give rise to differentiated tumor cells and to predict tumor recurrence and metastases, i.e., CSCs may be metastatic precursors. In this study, we show that ectopic overexpression of CD133 in OSCC cell lines KB, YD9, and YD10B cells significantly promotes the EMT and acquisition of stemness properties. CSC properties were analyzed by colony-formation assay and measurement of OCT4, SOX2, and NANOG expression, and the EMT was monitored by cell migration, a cell invasion assay, and analysis of E-cadherin, N-cadherin, and vimentin expression. CD133 overexpression led to formation of irregular spheroid colonies consistent with a stem cell phenotype and increased the expression of OCT4, SOX2, NANOG, N-cadherin, and vimentin. Taken together, these findings show that elevated levels of CD133 lead to OSCC invasiveness and metastasis, associated with the upregulation of EMT and stemness markers.

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References

  1. Haddad RI, Shin DM (2008) Recent advances in head and neck cancer. N Engl J Med 359(11):1143–1154

    Article  CAS  PubMed  Google Scholar 

  2. Jemal A et al (2008) Cancer statistics. CA Cancer J Clin 58(2):71–96

    Article  PubMed  Google Scholar 

  3. Pantel K, Brakenhoff RH (2004) Dissecting the metastatic cascade. Nat Rev Cancer 4(6):448–456

    Article  CAS  PubMed  Google Scholar 

  4. DiTroia JF (1972) Nodal metastases and prognosis in carcinoma of the oral cavity. Otolaryngol Clin N Am 5(2):333–342

    CAS  Google Scholar 

  5. Roepman P et al (2005) An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nat Genet 37(2):182–186

    Article  CAS  PubMed  Google Scholar 

  6. Noguti J et al (2012) Metastasis from oral cancer: an overview. Cancer Gen Proteomics 9(5):329–335

    CAS  Google Scholar 

  7. Hirshberg A et al (2008) Metastatic tumours to the oral cavity—pathogenesis and analysis of 673 cases. Oral Oncol 44(8):743–752

    Article  PubMed  Google Scholar 

  8. Ho CM et al (1992) Occult lymph node metastasis in small oral tongue cancers. Head Neck 14(5):359–363

    Article  CAS  PubMed  Google Scholar 

  9. Visvader JE, Lindeman GJ (2008) Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8(10):755–768

    Article  CAS  PubMed  Google Scholar 

  10. Tirino V et al (2008) Detection and characterization of CD133 + cancer stem cells in human solid tumours. PloS One 3(10):e3469

    Article  PubMed  PubMed Central  Google Scholar 

  11. Liu S et al (2015) G9a is essential for EMT-mediated metastasis and maintenance of cancer stem cell-like characters in head and neck squamous cell carcinoma. Oncotarget 6(9):6887–6901

    Article  PubMed  PubMed Central  Google Scholar 

  12. Angelastro JM, Lame MW (2010) Overexpression of CD133 promotes drug resistance in C6 glioma cells. Mol Cancer Res MCR 8(8):1105–1115

    Article  CAS  PubMed  Google Scholar 

  13. Zhang Q et al (2010) A subpopulation of CD133(+) cancer stem-like cells characterized in human oral squamous cell carcinoma confer resistance to chemotherapy. Cancer Lett 289(2):151–160

    Article  CAS  PubMed  Google Scholar 

  14. Corbeil D et al (2000) The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. J Biol Chem 275(8):5512–5520

    Article  CAS  PubMed  Google Scholar 

  15. Hilbe W et al (2004) CD133 positive endothelial progenitor cells contribute to the tumour vasculature in non-small cell lung cancer. J Clin Pathol 57(9):965–969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hemmati HD et al (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 100(25):15178–15183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chu P et al (2009) Characterization of a subpopulation of colon cancer cells with stem cell-like properties. Int J Cancer 124(6):1312–1321

    Article  CAS  PubMed  Google Scholar 

  18. Chiou SH et al (2008) Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res 14(13):4085–4095

    Article  CAS  PubMed  Google Scholar 

  19. Carvalho AL et al (2005) Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer 114(5):806–816

    Article  CAS  PubMed  Google Scholar 

  20. Yang CC et al (2013) Membrane type 1 matrix metalloproteinase induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells. BMC Cancer 13:171

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chen C et al (2011) Evidence for epithelial-mesenchymal transition in cancer stem cells of head and neck squamous cell carcinoma. PloS One 6(1):e16466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Micalizzi DS, Farabaugh SM, Ford HL (2010) Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol Neoplas 15(2):117–134

    Article  Google Scholar 

  23. Xu MH et al (2014) EMT and acquisition of stem cell-like properties are involved in spontaneous formation of tumorigenic hybrids between lung cancer and bone marrow-derived mesenchymal stem cells. PloS One 9(2):e87893

    Article  PubMed  PubMed Central  Google Scholar 

  24. Bernards R, Weinberg RA (2002) A progression puzzle. Nature 418:823

    Article  CAS  PubMed  Google Scholar 

  25. Kang HJ, Jang YJ (2012) Selective apoptotic effect of Zelkova serrata twig extract on mouth epidermoid carcinoma through p53 activation. Int J Or Sci 4(2):78–84

    Article  PubMed Central  Google Scholar 

  26. Lee EJ et al (2005) Characterization of newly established oral cancer cell lines derived from six squamous cell carcinoma and two mucoepidermoid carcinoma cells. Exp Mol Med 37(5):379–390

    Article  CAS  PubMed  Google Scholar 

  27. Pang LY et al (2012) Identification of tumour initiating cells in feline head and neck squamous cell carcinoma and evidence for gefitinib induced epithelial to mesenchymal transition. Vet J 193(1):46–52

    Article  CAS  PubMed  Google Scholar 

  28. Zhou BB et al (2009) Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov 8(10):806–823

    Article  CAS  PubMed  Google Scholar 

  29. Uchida N et al (2000) Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA 97(26):14720–14725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Iannolo G et al (2008) Apoptosis in normal and cancer stem cells. Crit Rev Oncol Hematol 66(1):42–51

    Article  PubMed  Google Scholar 

  31. Mizrak D, Brittan M, Alison M (2008) CD133: molecule of the moment. J Pathol 214(1):3–9

    Article  CAS  PubMed  Google Scholar 

  32. Bourguignon LY et al (2012) Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma. J Biol Chem 287(39):32800–32824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gangopadhyay S et al (2013) Breast cancer stem cells: a novel therapeutic target. Clin Breast Cancer 13(1):7–15

    Article  CAS  PubMed  Google Scholar 

  34. Mani SA et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This study was supported by research funds from Chosun University (2014). The authors declare that they have no conflicts of interest.

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Correspondence to Wonbong Lim.

Additional information

YeonHee Moon and Donghwi Kim have contributed equally to this work.

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Moon, Y., Kim, D., Sohn, H. et al. Effect of CD133 overexpression on the epithelial-to-mesenchymal transition in oral cancer cell lines. Clin Exp Metastasis 33, 487–496 (2016). https://doi.org/10.1007/s10585-016-9793-y

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  • DOI: https://doi.org/10.1007/s10585-016-9793-y

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