Human Cell Transformation pp 105-118

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 720)

Cancer Stem Cells, Models of Study and Implications of Therapy Resistance Mechanisms



There is now compelling evidence for tumour initiating or cancer stem cells (CSCs) in human cancers. The current evidence of this CSC hypothesis, the CSC phenotype and methods of identification, culture and in vitro modelling will be presented, with an emphasis on prostate cancer. Inherent in the CSC hypothesis is their dual role, as a tumour-initiating cell, and as a source of treatment-resistant cells; the mechanisms behind therapeutic resistance will be discussed. Such resistance is a consequence of the unique CSC phenotype, which differs from the differentiated progeny, which make up the bulk of a tumour. It seems that to target the whole tumour, employing traditional therapies to target bulk populations alongside targeted CSC-specific drugs, provides the best hope of lasting treatment or even cure.


  1. 1.
    Cairns J (1975) Mutation selection and the natural history of cancer. Nature 255(5505):197–200PubMedGoogle Scholar
  2. 2.
    Chury Z, Tobiska J (1958) [Clinical findings & results of culture in a case of stem-cell leukemia with pluripotential properties of the stem cells.]. Neoplasma 5(3):220–231PubMedGoogle Scholar
  3. 3.
    Furth J, Kahn MC (1937) The transmission of ­leukaemia of mice with a single cell. Am J Cancer 31:276–282Google Scholar
  4. 4.
    Hamburger AW, Salmon SE (1977) Primary bioassay of human tumor stem cells. Science 197(4302):461–463PubMedGoogle Scholar
  5. 5.
    Huntly BJ, Gilliland DG (2005) Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 5(4):311–321PubMedGoogle Scholar
  6. 6.
    Houghton J et al (2007) Stem cells and cancer. Semin Cancer Biol 17(3):191–203PubMedGoogle Scholar
  7. 7.
    Lee JT, Herlyn M (2007) Old disease, new culprit: tumor stem cells in cancer. J Cell Physiol 213(3):603–609PubMedGoogle Scholar
  8. 8.
    Polyak K, Hahn WC (2006) Roots and stems: stem cells in cancer. Nat Med 12(3):296–300PubMedGoogle Scholar
  9. 9.
    Wicha MS, Liu S, Dontu G (2006) Cancer stem cells: an old idea–a paradigm shift. Cancer Res 66(4):1883–1890, discussion 1895–1896PubMedGoogle Scholar
  10. 10.
    Farrell A et al (2006) Nature milestones: cancer. Nat 440: S7–S23Google Scholar
  11. 11.
    Lapidot T et al (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648PubMedGoogle Scholar
  12. 12.
    Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3(7):730–737PubMedGoogle Scholar
  13. 13.
    Matsui W et al (2004) Characterization of clonogenic multiple myeloma cells. Blood 103(6):2332–2336PubMedGoogle Scholar
  14. 14.
    Castor A et al (2005) Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia. Nat Med 11(6):630–637PubMedGoogle Scholar
  15. 15.
    Cox CV et al (2004) Characterization of acute ­lymphoblastic leukemia progenitor cells. Blood 104(9):2919–2925PubMedGoogle Scholar
  16. 16.
    Cox CV et al (2007) Characterization of a progenitor cell population in childhood T-cell acute lymphoblastic leukemia. Blood 109(2):674–682PubMedGoogle Scholar
  17. 17.
    Ricci-Vitiani L et al (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111–115PubMedGoogle Scholar
  18. 18.
    Al-Hajj M et al (2004) Therapeutic implications of cancer stem cells. Curr Opin Genet Dev 14(1):43–47PubMedGoogle Scholar
  19. 19.
    Collins AT et al (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65(23):10946–10951PubMedGoogle Scholar
  20. 20.
    Singh SK et al (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828PubMedGoogle Scholar
  21. 21.
    Singh SK et al (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401PubMedGoogle Scholar
  22. 22.
    Chan KS et al (2009) Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci U S A 106(33):14016–14021PubMedGoogle Scholar
  23. 23.
    Boiko AD et al (2010) Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271. Nature 466(7302):133–137PubMedGoogle Scholar
  24. 24.
    Schatton T et al (2008) Identification of cells initiating human melanomas. Nature 451(7176):345–349PubMedGoogle Scholar
  25. 25.
    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):4085–4095PubMedGoogle Scholar
  26. 26.
    Prince ME et al (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 104(3):973–978PubMedGoogle Scholar
  27. 27.
    Ma S et al (2007) Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 132(7):2542–2556PubMedGoogle Scholar
  28. 28.
    Bussolati B et al (2008) Identification of a tumor-initiating stem cell population in human renal carcinomas. Faseb J 22(10):3696–3705PubMedGoogle Scholar
  29. 29.
    Li C et al (2007) Identification of pancreatic cancer stem cells. Cancer Res 67(3):1030–1037PubMedGoogle Scholar
  30. 30.
    Zhang S et al (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68(11):4311–4320PubMedGoogle Scholar
  31. 31.
    Eramo A et al (2008) Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 15(3):504–514PubMedGoogle Scholar
  32. 32.
    Rutella S et al (2009) Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors. Clin Cancer Res 15(13):4299–4311PubMedGoogle Scholar
  33. 33.
    Alison MR, Islam S (2009) Attributes of adult stem cells. J Pathol 217(2):144–160PubMedGoogle Scholar
  34. 34.
    Kuci S et al (2009) Adult stem cells as an alternative source of multipotential (pluripotential) cells in regenerative medicine. Curr Stem Cell Res Ther 4(2):107–117PubMedGoogle Scholar
  35. 35.
    Wang Y, Armstrong SA (2008) Cancer: inappropriate expression of stem cell programs? Cell Stem Cell 2(4):297–299PubMedGoogle Scholar
  36. 36.
    Zhang H, Wang ZZ (2008) Mechanisms that mediate stem cell self-renewal and differentiation. J Cell Biochem 103(3):709–718PubMedGoogle Scholar
  37. 37.
    Clarke MF et al (2006) Cancer stem cells–perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66(19):9339–9344PubMedGoogle Scholar
  38. 38.
    Jordan CT (2009) Cancer stem cells: controversial or just misunderstood? Cell Stem Cell 4(3):203–205PubMedGoogle Scholar
  39. 39.
    Aasen T et al (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26(11):1276–1284PubMedGoogle Scholar
  40. 40.
    Park IH et al (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451(7175):141–146PubMedGoogle Scholar
  41. 41.
    Takahashi K et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872PubMedGoogle Scholar
  42. 42.
    Yu J et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920PubMedGoogle Scholar
  43. 43.
    Maitland NJ, Collins AT (2010) Cancer stem cells – a therapeutic target? Curr Opin Mol Therap 12(6):662–673Google Scholar
  44. 44.
    Quintana E et al (2008) Efficient tumour formation by single human melanoma cells. Nature 456(7222):593–598PubMedGoogle Scholar
  45. 45.
    Ishizawa K et al (2010) Tumor-initiating cells are rare in many human tumors. Cell Stem Cell 7(3):279–282PubMedGoogle Scholar
  46. 46.
    Michor F et al (2005) Dynamics of chronic myeloid leukaemia. Nature 435(7046):1267–1270PubMedGoogle Scholar
  47. 47.
    Garvalov BK, Acker T (2011) Cancer stem cells: a new framework for the design of tumor therapies. J Mol Med 89:95–107. doi: 10.1007/s00109-010-0685-3Google Scholar
  48. 48.
    Hermann PC et al (2010) Cancer stem cells in solid tumors. Semin Cancer Biol 20(2):77–84PubMedGoogle Scholar
  49. 49.
    Visvader JE, Lindeman GJ (2008) Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8(10):755–768PubMedGoogle Scholar
  50. 50.
    Park PC et al (2007) Stem cell enrichment approaches. Semin Cancer Biol 17(3):257–264PubMedGoogle Scholar
  51. 51.
    Zhao RC, Zhu YS, Shi Y (2008) New hope for cancer treatment: exploring the distinction between normal adult stem cells and cancer stem cells. Pharmacol Ther 119(1):74–82PubMedGoogle Scholar
  52. 52.
    Mimeault M et al (2008) Functions of normal and malignant prostatic stem/progenitor cells in tissue regeneration and cancer progression and novel targeting therapies. Endocr Rev 29(2):234–252PubMedGoogle Scholar
  53. 53.
    Birnie R et al (2008) Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions. Genome Biol 9(5):R83PubMedGoogle Scholar
  54. 54.
    Blum R et al (2009) Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer. PLoS One 4(5):e5722PubMedGoogle Scholar
  55. 55.
    Sakariassen PO, Immervoll H, Chekenya M (2007) Cancer stem cells as mediators of treatment resistance in brain tumors: status and controversies. Neoplasia 9(11):882–892PubMedGoogle Scholar
  56. 56.
    Gupta PB, Chaffer CL, Weinberg RA (2009) Cancer stem cells: mirage or reality? Nat Med 15(9):1010–1012PubMedGoogle Scholar
  57. 57.
    Frame FM et al (2010) Development and limitations of lentivirus vectors as tools for tracking differentiation in prostate epithelial cells. Exp Cell Res 316(19):3161–3171PubMedGoogle Scholar
  58. 58.
    Hope KJ, Jin L, Dick JE (2004) Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 5(7):738–743PubMedGoogle Scholar
  59. 59.
    Wang X et al (2009) A luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature 461(7263):495–500PubMedGoogle Scholar
  60. 60.
    Leong KG et al (2008) Generation of a prostate from a single adult stem cell. Nature 456(7223):804–808PubMedGoogle Scholar
  61. 61.
    Robinson EJ, Neal DE, Collins AT (1998) Basal cells are progenitors of luminal cells in primary cultures of differentiating human prostatic epithelium. Prostate 37(3):149–160PubMedGoogle Scholar
  62. 62.
    Richardson GD et al (2004) CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci 117(Pt 16):3539–3545PubMedGoogle Scholar
  63. 63.
    Trerotola M et al (2010) CD133, Trop-2 and alpha2beta1 integrin surface receptors as markers of putative human prostate cancer stem cells. Am J Transl Res 2(2):135–144PubMedGoogle Scholar
  64. 64.
    Goldstein AS et al (2010) Identification of a cell of origin for human prostate cancer. Science 329(5991):568–571PubMedGoogle Scholar
  65. 65.
    Goldstein AS, Stoyanova T, Witte ON (2010) Primitive origins of prostate cancer: in vivo evidence for prostate-regenerating cells and prostate cancer-initiating cells. Mol Oncol 4(5):385–396PubMedGoogle Scholar
  66. 66.
    Lawson DA et al (2010) Basal epithelial stem cells are efficient targets for prostate cancer initiation. Proc Natl Acad Sci U S A 107(6):2610–2615PubMedGoogle Scholar
  67. 67.
    Patrawala L et al (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25(12):1696–1708PubMedGoogle Scholar
  68. 68.
    Patrawala L et al (2007) Hierarchical organization of prostate cancer cells in xenograft tumors: the CD44+alpha2beta1+ cell population is enriched in tumor-initiating cells. Cancer Res 67(14):6796–6805PubMedGoogle Scholar
  69. 69.
    Tang DG et al (2007) Prostate cancer stem/progenitor cells: identification, characterization, and implications. Mol Carcinog 46(1):1–14PubMedGoogle Scholar
  70. 70.
    Maitland NJ et al (2010) Prostate cancer stem cells: Do they have a basal or luminal phenotype? Horm Cancer 2(1):47–61Google Scholar
  71. 71.
    Loberg RD et al (2006) Development of the VCaP androgen-independent model of prostate cancer. Urol Oncol 24(2):161–168PubMedGoogle Scholar
  72. 72.
    Guo R et al (2011) Description of the CD133+ subpopulation of the human ovarian cancer cell line OVCAR3. Oncol Rep 25(1):141–146PubMedGoogle Scholar
  73. 73.
    Yeung TM et al (2010) Cancer stem cells from ­colorectal cancer-derived cell lines. Proc Natl Acad Sci U S A 107(8):3722–3727PubMedGoogle Scholar
  74. 74.
    Liu T et al (2010) Establishment and characterization of multi-drug resistant, prostate carcinoma-­initiating stem-like cells from human prostate cancer cell lines 22RV1. Mol Cell Biochem 340(1–2):265–273PubMedGoogle Scholar
  75. 75.
    Maitland NJ et al (2010) Gene transfer vectors targeted to human prostate cancer: do we need better preclinical testing systems? Hum Gene Ther 21(7):815–827PubMedGoogle Scholar
  76. 76.
    Miki J et al (2007) Identification of putative stem cell markers, CD133 and CXCR4, in hTERT-­immortalized primary nonmalignant and malignant tumor-derived human prostate epithelial cell lines and in prostate cancer specimens. Cancer Res 67(7):3153–3161PubMedGoogle Scholar
  77. 77.
    Swift SL, Burns JE, Maitland NJ (2010) Altered expression of neurotensin receptors is associated with the differentiation state of prostate cancer. Cancer Res 70(1):347–356PubMedGoogle Scholar
  78. 78.
    Hirschhaeuser F et al (2010) Multicellular tumor spheroids: an underestimated tool is catching up again. J Biotechnol 148(1):3–15PubMedGoogle Scholar
  79. 79.
    Lang SH et al (2001) Prostate epithelial cell lines form spheroids with evidence of glandular differentiation in three-dimensional Matrigel cultures. Br J Cancer 85(4):590–599PubMedGoogle Scholar
  80. 80.
    Lang SH et al (2001) Experimental prostate epithelial morphogenesis in response to stroma and three-dimensional matrigel culture. Cell Growth Differ 12(12):631–640PubMedGoogle Scholar
  81. 81.
    Lang SH et al (2010) Modeling the prostate stem cell niche: an evaluation of stem cell survival and expansion in vitro. Stem Cells Dev 19(4):537–546PubMedGoogle Scholar
  82. 82.
    Sneddon JB, Werb Z (2007) Location, location, ­location: the cancer stem cell niche. Cell Stem Cell 1(6):607–611PubMedGoogle Scholar
  83. 83.
    Li L, Neaves WB (2006) Normal stem cells and ­cancer stem cells: the niche matters. Cancer Res 66(9):4553–4557PubMedGoogle Scholar
  84. 84.
    Josson S et al (2010) Tumor-stroma co-evolution in prostate cancer progression and metastasis. Semin Cell Dev Biol 21(1):26–32PubMedGoogle Scholar
  85. 85.
    van der Pluijm G (2011) Epithelial plasticity, cancer stem cells and bone metastasis formation. Bone 48(1):37–43PubMedGoogle Scholar
  86. 86.
    Iwatsuki M et al (2010) Epithelial-mesenchymal transition in cancer development and its clinical ­significance. Cancer Sci 101(2):293–299PubMedGoogle Scholar
  87. 87.
    Micalizzi DS, Farabaugh SM, Ford HL (2010) Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor ­progression. J Mammary Gland Biol Neoplasia 15(2):117–134PubMedGoogle Scholar
  88. 88.
    Elliott A, Adams J, Al-Hajj M (2010) The ABCs of cancer stem cell drug resistance. IDrugs 13(9):632–635PubMedGoogle Scholar
  89. 89.
    Scotto KW (2003) Transcriptional regulation of ABC drug transporters. Oncogene 22(47):7496–7511PubMedGoogle Scholar
  90. 90.
    Tanei T et al (2009) Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast ­cancers. Clin Cancer Res 15(12):4234–4241PubMedGoogle Scholar
  91. 91.
    Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5(4):275–284PubMedGoogle Scholar
  92. 92.
    Ding XW, Wu JH, Jiang CP (2010) ABCG2: a potential marker of stem cells and novel target in stem cell and cancer therapy. Life Sci 86(17–18):631–637PubMedGoogle Scholar
  93. 93.
    Ma I, Allan AL (2011) The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev 7:292–306. doi: 10.1007/s12015-010-9208-4Google Scholar
  94. 94.
    Ginestier C et al (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555–567PubMedGoogle Scholar
  95. 95.
    Gatti L et al (2009) ABC transporters as potential targets for modulation of drug resistance. Mini Rev Med Chem 9(9):1102–1112PubMedGoogle Scholar
  96. 96.
    Fletcher JI et al (2010) ABC transporters in cancer: more than just drug efflux pumps. Nat Rev Cancer 10(2):147–156PubMedGoogle Scholar
  97. 97.
    Wu CP, Calcagno AM, Ambudkar SV (2008) Reversal of ABC drug transporter-mediated multidrug resistance in cancer cells: evaluation of current strategies. Curr Mol Pharmacol 1(2):93–105PubMedGoogle Scholar
  98. 98.
    Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70PubMedGoogle Scholar
  99. 99.
    Ishii H et al (2008) Cancer stem cells and chemoradiation resistance. Cancer Sci 99(10):1871–1877PubMedGoogle Scholar
  100. 100.
    Morrison R et al (2011) Targeting the mechanisms of resistance to chemotherapy and radiotherapy with the cancer stem cell hypothesis. J Oncol 2011:941876. doi: 10:1155/2011/941876Google Scholar
  101. 101.
    Bao S et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444(7120):756–760PubMedGoogle Scholar
  102. 102.
    Sheehan JP et al (2010) Improving the radiosensitivity of radioresistant and hypoxic glioblastoma. Future Oncol 6(10):1591–1601PubMedGoogle Scholar
  103. 103.
    Viale A et al (2009) Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells. Nature 457(7225):51–56PubMedGoogle Scholar
  104. 104.
    Mohrin M et al (2010) Hematopoietic stem cell ­quiescence promotes error-prone DNA repair and mutagenesis. Cell Stem Cell 7(2):174–185PubMedGoogle Scholar
  105. 105.
    Diehn M et al (2009) Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458(7239):780–783PubMedGoogle Scholar
  106. 106.
    Facchino S et al (2010) BMI1 confers radioresistance to normal and cancerous neural stem cells through recruitment of the DNA damage response machinery. J Neurosci 30(30):10096–10111PubMedGoogle Scholar
  107. 107.
    Fulda S, Pervaiz S (2010) Apoptosis signaling in cancer stem cells. Int J Biochem Cell Biol 42(1):31–38PubMedGoogle Scholar
  108. 108.
    Liu G et al (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 5:67PubMedGoogle Scholar
  109. 109.
    Baud V, Karin M (2009) Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov 8(1):33–40PubMedGoogle Scholar
  110. 110.
    Guzman ML et al (2007) An orally bioavailable ­parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells. Blood 110(13):4427–4435PubMedGoogle Scholar
  111. 111.
    Domen J, Cheshier SH, Weissman IL (2000) The role of apoptosis in the regulation of hematopoietic stem cells: Overexpression of Bcl-2 increases both their number and repopulation potential. J Exp Med 191(2):253–264PubMedGoogle Scholar
  112. 112.
    Tagscherer KE et al (2008) Apoptosis-based treatment of glioblastomas with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins. Oncogene 27(52):6646–6656PubMedGoogle Scholar
  113. 113.
    Takebe N et al (2011) Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol 8:97–106. doi: 10.1038/nrclinonc.2010.196Google Scholar
  114. 114.
    Grudzien P et al (2010) Inhibition of Notch signaling reduces the stem-like population of breast cancer cells and prevents mammosphere formation. Anticancer Res 30(10):3853–3867PubMedGoogle Scholar
  115. 115.
    Fan X et al (2010) NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells 28(1):5–16PubMedGoogle Scholar
  116. 116.
    Woodward WA et al (2007) WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci U S A 104(2):618–623PubMedGoogle Scholar
  117. 117.
    Mueller MT et al (2009) Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. Gastroenterology 137(3):1102–1113PubMedGoogle Scholar
  118. 118.
    Sarkar FH et al (2010) Implication of microRNAs in drug resistance for designing novel cancer therapy. Drug Resist Updat 13(3):57–66PubMedGoogle Scholar
  119. 119.
    Hatfield S, Ruohola-Baker H (2008) microRNA and stem cell function. Cell Tissue Res 331(1):57–66PubMedGoogle Scholar
  120. 120.
    Shcherbata HR et al (2006) The MicroRNA pathway plays a regulatory role in stem cell division. Cell Cycle 5(2):172–175PubMedGoogle Scholar
  121. 121.
    Hatfield SD et al (2005) Stem cell division is regulated by the microRNA pathway. Nature 435(7044):974–978PubMedGoogle Scholar
  122. 122.
    Ji Q et al (2010) No small matter: microRNAs – key regulators of cancer stem cells. Int J Clin Exp Med 3(1):84–87PubMedGoogle Scholar
  123. 123.
    Ji Q et al (2009) MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS One 4(8):e6816PubMedGoogle Scholar
  124. 124.
    Kong D et al (2010) Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS One 5(8):e12445PubMedGoogle Scholar
  125. 125.
    Starnes LM, Sorrentino A (2011) Regulatory circuitries coordinated by transcription factors and microRNAs at the cornerstone of hematopoietic stem cell self-renewal and differentiation. Curr Stem Cell Res Ther 6:142–161PubMedGoogle Scholar
  126. 126.
    Dylla SJ et al (2008) Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One 3(6):e2428PubMedGoogle Scholar
  127. 127.
    Phillips TM, McBride WH, Pajonk F (2006) The response of CD24(-/low)/CD44+ breast cancer-­initiating cells to radiation. J Natl Cancer Inst 98(24):1777–1785PubMedGoogle Scholar
  128. 128.
    Calcagno AM et al (2010) Prolonged drug selection of breast cancer cells and enrichment of cancer stem cell characteristics. J Natl Cancer Inst 102(21):1637–1652PubMedGoogle Scholar
  129. 129.
    Creighton CJ et al (2009) Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci U S A 106(33):13820–13825PubMedGoogle Scholar
  130. 130.
    Enver T et al (2009) Stem cell states, fates, and the rules of attraction. Cell Stem Cell 4(5):387–397PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Biology, YCR Cancer Research UnitUniversity of YorkHeslingtonUK
  2. 2.YCR Cancer Research Unit, Department of BiologyUniversity of YorkHeslingtonUK

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