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Nat Commun. 2011 Jan 18;2:162. doi: 10.1038/ncomms1159.

Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-κB signalling.

Nature communications

Vinagolu K Rajasekhar, Lorenz Studer, William Gerald, Nicholas D Socci, Howard I Scher

Affiliations

  1. 1] Stem Cell Center and Developmental Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. [2] Sidney Kimmel Center for Prostate and Urologic Cancers, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.

PMID: 21245843 PMCID: PMC3105310 DOI: 10.1038/ncomms1159

Abstract

Androgen depletion is a key strategy for treating human prostate cancer, but the presence of hormone-independent cells escaping treatment remains a major therapeutic challenge. Here, we identify a minor subset of stem-like human prostate tumour-initiating cells (TICs) that do not express prostate cancer markers, such as androgen receptor or prostate specific antigen. These TICs possess stem cell characteristics and multipotency as demonstrated by in vitro sphere-formation and in vivo tumour-initiation, respectively. The cells represent an undifferentiated subtype of basal cells and can be purified from prostate tumours based on coexpression of the human pluripotent stem cell marker TRA-1-60 with CD151 and CD166. Such triple-marker-positive TICs recapitulate the original parent tumour heterogeneity in serial xeno-transplantations indicating a tumour cell hierarchy in human prostate cancer development. These TICs exhibit increased nuclear factor-κB activity. These findings are important in understanding the molecular basis of human prostate cancer.

References

  1. Nature. 2009 Nov 5;462(7269):104-7 - PubMed
  2. Adv Exp Med Biol. 2008;617:547-55 - PubMed
  3. Stem Cells. 2008 Jan;26(1):292-8 - PubMed
  4. J Immunol. 1998 Oct 15;161(8):3902-11 - PubMed
  5. Nature. 2001 Nov 1;414(6859):105-11 - PubMed
  6. Am J Respir Cell Mol Biol. 1998 Jun;18(6):860-6 - PubMed
  7. Mol Ther. 2009 Feb;17(2):219-30 - PubMed
  8. Genome Biol. 2008;9(5):R83 - PubMed
  9. J Anat. 2002 Mar;200(Pt 3):249-58 - PubMed
  10. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63 - PubMed
  11. Am J Pathol. 2003 May;162(5):1529-37 - PubMed
  12. Nature. 2009 Sep 24;461(7263):495-500 - PubMed
  13. Semin Cancer Biol. 2007 Jun;17(3):219-24 - PubMed
  14. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2610-5 - PubMed
  15. EMBO J. 2004 Jun 16;23(12):2369-80 - PubMed
  16. Nat Protoc. 2009;4(1):44-57 - PubMed
  17. Prostate. 2008 Jun 15;68(9):1025-34 - PubMed
  18. Cell. 2009 Nov 13;139(4):693-706 - PubMed
  19. Science. 2010 Jul 30;329(5991):568-71 - PubMed
  20. Cancer Epidemiol Biomarkers Prev. 2004 Nov;13(11 Pt 1):1717-21 - PubMed
  21. Clin Cancer Res. 2004 Dec 15;10(24):8460-4 - PubMed
  22. Prostate. 2010 Apr 1;70(5):491-501 - PubMed
  23. Science. 2009 Jun 26;324(5935):1670-3 - PubMed
  24. Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11355-60 - PubMed
  25. Prostate. 1996 Feb;28(2):98-106 - PubMed
  26. Cancer Res. 2007 Feb 1;67(3):967-75 - PubMed
  27. Blood. 2008 Dec 15;112(13):4793-807 - PubMed
  28. Prostate. 2003 May 15;55(3):206-18 - PubMed
  29. Mol Cell. 2003 Oct;12(4):889-901 - PubMed
  30. Prostate. 2002 May 1;51(2):98-107 - PubMed
  31. Mol Biol Cell. 1997 Feb;8(2):313-23 - PubMed
  32. Cancer Res. 2005 Dec 1;65(23):10946-51 - PubMed
  33. Prostate. 2008 Jun 15;68(9):1007-24 - PubMed
  34. Differentiation. 2005 Dec;73(9-10):463-73 - PubMed
  35. Nat Rev Cancer. 2008 Oct;8(10):755-68 - PubMed
  36. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12543-8 - PubMed
  37. Biochem Biophys Res Commun. 2006 Sep 8;347(4):1158-65 - PubMed
  38. J Clin Invest. 2008 Jun;118(6):2021-4 - PubMed
  39. Nat Rev Cancer. 2006 Aug;6(8):637-45 - PubMed
  40. J Biol Chem. 1996 Sep 27;271(39):24151-6 - PubMed
  41. J Clin Oncol. 2008 Jun 10;26(17):2862-70 - PubMed
  42. Biol Reprod. 1999 May;60(5):1257-62 - PubMed
  43. Mol Cell Biol. 2003 Oct;23(19):7068-81 - PubMed
  44. Cancer Res. 1994 Dec 1;54(23):6049-52 - PubMed
  45. Curr Opin Genet Dev. 2008 Feb;18(1):19-26 - PubMed
  46. Cancer Res. 2006 Oct 1;66(19):9339-44 - PubMed
  47. Development. 2004 Oct;131(20):4955-64 - PubMed
  48. J Clin Oncol. 2008 Mar 1;26(7):1148-59 - PubMed
  49. Cancer Res. 2007 Jan 15;67(2):528-36 - PubMed
  50. Int J Urol. 2010 Feb;17(2):139-47 - PubMed
  51. Nat Med. 2007 May;13(5):642-8 - PubMed
  52. Nature. 2008 Dec 11;456(7223):804-8 - PubMed
  53. J Mol Med (Berl). 2008 Sep;86(9):1025-32 - PubMed
  54. Br J Cancer. 2010 Mar 30;102(7):1163-73 - PubMed
  55. Annu Rev Cell Dev Biol. 2007;23:675-99 - PubMed
  56. PLoS One. 2009 May 22;4(5):e5662 - PubMed
  57. Cancer Res. 1992 Nov 15;52(22):6182-7 - PubMed

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