Display options
Share it on

Oncol Lett. 2015 Apr;9(4):1641-1646. doi: 10.3892/ol.2015.2918. Epub 2015 Jan 29.

Metastatic colon cancer cell populations contain more cancer stem-like cells with a higher susceptibility to natural killer cell-mediated lysis compared with primary colon cancer cells.

Oncology letters

Ga Rim Kim, Ga-Hee Ha, Jae-Ho Bae, Sae-Ock Oh, Sun-Hee Kim, Chi-Dug Kang

Affiliations

  1. Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626-870, Republic of Korea.
  2. Department of Anatomy, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626-870, Republic of Korea.

PMID: 25789015 PMCID: PMC4356422 DOI: 10.3892/ol.2015.2918

Abstract

In the present study, the soft agar clonogenicity and the susceptibility of clonogenic cancer cells to natural killer (NK) cells were compared between primary colon cancer cells (KM12C) and metastatic colon cancer cells (KM12L4a and KM12SM) to determine whether the metastatic cancer cells consisted of more cancer stem-like cells and were resistant to NK cell-mediated lysis. The majority of colon cancer cells were positive for putative cancer stem cell markers, including CD44, CD133 and EpCAM, with the exception of KM12C cells, of which only ~55% were positive for CD133. In addition, the expression levels of sex determining region Y-box 2, Nanog and octamer-binding transcription factor 4, which are essential for maintaining self-renewal, were higher in KM12L4a and KM12SM compared with that in KM12C cells. Consistently, an increased clonogenicity of KM12L4a and KM12SM compared with KM12C cells in soft agar was observed. The expression levels of NKG2D ligands, including major histocompatibility complex class I polypeptide-related sequence A/B and UL16 binding protein 2, and of death receptor 5 were significantly higher in KM12L4a and KM12SM than in KM12C cells. Furthermore, the results indicated an increased susceptibility of KM12L4a and KM12SM to NK cell-mediated cytotoxicity in comparison with KM12C cells. These results indicated that metastatic colon cancer cell populations may consist of more cancer stem-like cells, and have greater susceptibility to NK cell-mediated lysis compared with that of primary colon cancers.

Keywords: DR5; NKG2D ligands; clonogenicity; metastatic colon cancer cells; natural killer cell-mediated lysis

References

  1. Int Rev Immunol. 2008;27(3):93-110 - PubMed
  2. World J Gastroenterol. 2014 Jan 28;20(4):923-42 - PubMed
  3. Science. 2011 Mar 25;331(6024):1559-64 - PubMed
  4. Cancer Immunol Immunother. 2008 Oct;57(10):1541-52 - PubMed
  5. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63 - PubMed
  6. Mol Immunol. 2005 Feb;42(4):501-10 - PubMed
  7. Clin Exp Metastasis. 2002;19(2):175-80 - PubMed
  8. Mol Cancer Ther. 2012 Oct;11(10 ):2222-32 - PubMed
  9. J Pharmacol Exp Ther. 2004 Dec;311(3):1062-70 - PubMed
  10. J Immunol. 2013 Mar 1;190(5):2381-90 - PubMed
  11. J Immunother. 2008 Jun;31(5):475-86 - PubMed
  12. Methods. 2001 Dec;25(4):402-8 - PubMed
  13. Cell. 2008 Feb 22;132(4):567-82 - PubMed
  14. Nat Med. 2011 Mar;17(3):313-9 - PubMed
  15. J Clin Invest. 2008 Jun;118(6):2111-20 - PubMed
  16. Exp Mol Med. 2006 Oct 31;38(5):474-84 - PubMed
  17. Radiat Oncol. 2014 Mar 26;9(1):85 - PubMed
  18. Cancer Res. 1995 Jul 15;55(14):3123-31 - PubMed
  19. Acta Pharmacol Sin. 2013 Jun;34(6):732-40 - PubMed
  20. Nature. 2007 Jan 4;445(7123):106-10 - PubMed
  21. Cell Death Differ. 2014 Jan;21(1):5-14 - PubMed
  22. J Immunother. 2013 Jun;36(5):319-29 - PubMed
  23. Nat Rev Immunol. 2007 May;7(5):329-39 - PubMed
  24. Ann Surg Oncol. 2009 Dec;16(12 ):3488-98 - PubMed
  25. J Clin Invest. 2008 Jun;118(6):2021-4 - PubMed
  26. J Pathol. 2011 Jan;223(2):147-61 - PubMed
  27. Cell. 2006 Nov 17;127(4):679-95 - PubMed
  28. Front Immunol. 2012 Sep 25;3:299 - PubMed
  29. Int J Cancer. 2004 Jul 20;110(6):869-74 - PubMed
  30. Anticancer Res. 2001 Jul-Aug;21(4A):2329-39 - PubMed
  31. Br J Pharmacol. 2013 Aug;169(8):1723-44 - PubMed
  32. Annu Rev Immunol. 2013;31:227-58 - PubMed
  33. Nature. 2007 Jan 4;445(7123):111-5 - PubMed
  34. Annu Rev Immunol. 2013;31:413-41 - PubMed
  35. Cancer Res. 1988 Dec 1;48(23):6863-71 - PubMed
  36. Cancer Sci. 2012 Jan;103(1):7-16 - PubMed
  37. Cancer Res. 2001 Jan 1;61(1):333-8 - PubMed
  38. Science. 1977 Jul 29;197(4302):461-3 - PubMed
  39. PLoS One. 2010 May 19;5(5):e10714 - PubMed
  40. Clin Cancer Res. 2009 Nov 15;15(22):6993-7002 - PubMed

Publication Types