Advertisement

Tumor Biology

, Volume 32, Issue 3, pp 425–440 | Cite as

Cancer stem cells and cancer therapy

  • Sara Soltanian
  • Maryam M. Matin
Review

Abstract

Cancer stem cells (CSCs) are a subpopulation of tumour cells that possess the stem cell properties of self-renewal and differentiation. Stem cells might be the target cells responsible for malignant transformation, and tumour formation may be a disorder of stem cell self-renewal pathway. Epigenetic alterations and mutations of genes involved in signal transmissions may promote the formation of CSCs. These cells have been identified in many solid tumours including breast, brain, lung, prostate, testis, ovary, colon, skin, liver, and also in acute myeloid leukaemia. The CSC theory clarifies not only the issue of tumour initiation, development, metastasis and relapse, but also the ineffectiveness of conventional cancer therapies. Treatments directed against the bulk of the cancer cells may produce striking responses but they are unlikely to result in long-term remissions if the rare CSCs are not targeted. In this review, we consider the properties of CSCs and possible strategies for controlling the viability and tumourigenecity of these cells, including therapeutic models for selective elimination of CSCs and induction of their proper differentiation.

Keywords

Cancer stem cell Tumour Differentiation therapy Elimination therapy 

References

  1. 1.
    Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer and cancer stem cells. Nature. 2001;414:105–11.PubMedCrossRefGoogle Scholar
  2. 2.
    Tu SM, Lin SH, Logothetis CJ. Stem-cell origin of metastasis and heterogeneity in solid tumours. Lancet Oncol. 2002;3:508–13.PubMedCrossRefGoogle Scholar
  3. 3.
    Passegue E, Jamieson CH, Ailles LE, Weissman IL. Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics. Proc Natl Acad Sci USA. 2003;100:11842–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Lobo NA, Shimono Y, Qian D, Clarke MF. The biology of cancer stem cells. Annu Rev Cell Dev Biol. 2007;23:675–99.PubMedCrossRefGoogle Scholar
  5. 5.
    Virchow R. Editorial. Arch Pathol Anat Physiol Klin Med. 1855;8:23.Google Scholar
  6. 6.
    Sell S. Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol. 2004;51:1–28.PubMedCrossRefGoogle Scholar
  7. 7.
    Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumourigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100:3983–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.PubMedCrossRefGoogle Scholar
  10. 10.
    Fang B, Zheng C, Liao L, Han Q, Sun Z, Jiang X, et al. Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics. Blood. 2005;105:2733–40.PubMedCrossRefGoogle Scholar
  11. 11.
    Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA. 2007;104:973–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, et al. Identification of cells initiating human melanomas. Nature. 2008;451:345–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. 2008;13:153–66.PubMedCrossRefGoogle Scholar
  15. 15.
    Suvà ML, Riggi N, Stehle JC, Baumer K, Tercier S, Joseph JM, et al. Identification of cancer stem cells in Ewing's sarcoma. Cancer Res. 2009;69:1776–81.PubMedCrossRefGoogle Scholar
  16. 16.
    Boiko AD, Razorenova OV, van de Rijn M, Swetter SM, Johnson DL, Ly DP, et al. Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271. Nature. 2010;466:133–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Rasheed ZA, Yang J, Wang Q, Kowalski J, Freed I, Murter C, et al. Prognostic significance of tumourigenic cells with mesenchymal features in pancreatic adenocarcinoma. J Natl Cancer Inst. 2010;102:340–51.PubMedCrossRefGoogle Scholar
  18. 18.
    Kelly PN, Dakic A, Adams JM, Nutt SL, Strasser A. Tumour growth need not be driven by rare cancer stem cells. Science. 2007;317:337.PubMedCrossRefGoogle Scholar
  19. 19.
    Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ. Efficient tumour formation by single human melanoma cells. Nature. 2008;456:593–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Ishizawa K, Rasheed ZA, Karisch R, Wang Q, Kowalski J, Susky E, et al. Tumour initiating cells are rare in many human tomour. Cell Stem Cell. 2010;7:279–82.PubMedCrossRefGoogle Scholar
  21. 21.
    Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al. Identification of a cancer stem cell in human brain tumours. Cancer Res. 2003;63:5821–8.PubMedGoogle Scholar
  23. 23.
    Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005;121:823–35.PubMedCrossRefGoogle Scholar
  24. 24.
    Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, et al. Highly purified CD44+ prostate cancer cells from xenograft human tumours are enriched in tumourigenic and metastatic progenitor cells. Oncogene. 2006;25:1696–708.PubMedCrossRefGoogle Scholar
  25. 25.
    Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumourigenic prostate cancer stem cells. Cancer Res. 2005;65:10946–51.PubMedCrossRefGoogle Scholar
  26. 26.
    Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, et al. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian inhibiting substance responsiveness. Proc Natl Acad Sci USA. 2006;103:11154–9.PubMedCrossRefGoogle Scholar
  27. 27.
    O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106–10.PubMedCrossRefGoogle Scholar
  28. 28.
    Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon cancer-initiating cells. Nature. 2007;445:111–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Taylor G, Lehrer MS, Jensen PJ, Sun TT, Lavker RM. Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell. 2000;102:451–61.PubMedCrossRefGoogle Scholar
  30. 30.
    Blanpain C, Lowry WE, Geoghegan A, Polak L, Fuchs E. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell. 2004;118:635–48.PubMedCrossRefGoogle Scholar
  31. 31.
    Andrews PW, Matin M, Bahrami AR, Damjanov I, Gokhale P, Draper JS. Embryonic stem (ES) cells and embryonal carcinoma (EC) cells: opposite sides of the same coin. Biochem Soc Trans. 2005;33:1526–30.PubMedCrossRefGoogle Scholar
  32. 32.
    Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer. 2003;3:895–902.PubMedCrossRefGoogle Scholar
  33. 33.
    Lessard J, Sauvageau G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 2003;423:255–60.PubMedCrossRefGoogle Scholar
  34. 34.
    Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis. Nature. 2004;432:324–31.PubMedCrossRefGoogle Scholar
  35. 35.
    Al-Hajj M, Berker MW, Wicha M, Weissman I, Clarke MF. Therapeutic implications of cancer stem cells. Curr Opin Genet Dev. 2004;14:43–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–83.PubMedCrossRefGoogle Scholar
  37. 37.
    Ishii H, Iwatsuki M, Ieta K, Ohta D, Haraguchi N, Mimori K, et al. Cancer stem cells and chemoradiation resistance. Cancer Sci. 2008;99:1871–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Terpstra W, Ploemacher RE, Prins A, van Lom K, Pouwels K, Wognum AW, et al. Fluorouracil selectively spares acute myeloid leukemia cells with long-term growth abilities in immunodeficient mice and in culture. Blood. 1996;88:1944–50.PubMedGoogle Scholar
  39. 39.
    Ohyashiki JH, Sashida G, Tauchi T, Ohyashiki K. Telomeres and telomerase in hematologic neoplasia. Oncogene. 2002;21:680–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Ju Z, Rudolph KL. Telomeres and telomerase in stem cells during aging and disease. Genome Dyn. 2006;1:84–103.PubMedCrossRefGoogle Scholar
  41. 41.
    Rosner MH, Vigano MA, Ozato K, Timmons PM, Poirier F, Rigby PW, et al. A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature. 1990;345:686–92.PubMedCrossRefGoogle Scholar
  42. 42.
    Burdon T, Smith A, Savatier P. Signalling, cell cycle and pluripotency in embryonic stem cells. Trends Cell Biol. 2002;12:432–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Boiani M, Scholer HR. Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol. 2005;6:872–84.PubMedCrossRefGoogle Scholar
  44. 44.
    Matin MM, Walsh JR, Gokhale PJ, Draper JS, Bahrami AR, Morton I, et al. Specific knockdown of Oct4 and beta2-microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells. Stem Cells. 2004;22:659–68.PubMedCrossRefGoogle Scholar
  45. 45.
    Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, et al. Isolation and in vitro propagation of tumourigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 2005;65:5506–11.PubMedCrossRefGoogle Scholar
  46. 46.
    Chen YC, Hsu HS, Chen YW, Tsai TH, How CK, Wang CY, et al. Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133+ cells. PLoS One. 2008;3:e2637.PubMedCrossRefGoogle Scholar
  47. 47.
    Schoenhals M, Kassambara A, De Vos J, Hose D, Moreaux J, Klein B. Embryonic stem cell markers expression in cancers. Biochem Biophys Res Commun. 2009;383:157–62.PubMedCrossRefGoogle Scholar
  48. 48.
    Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2002;2:48–50.PubMedCrossRefGoogle Scholar
  49. 49.
    Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, et al. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 2001;7:1028–34.PubMedCrossRefGoogle Scholar
  50. 50.
    Van Stijn A, Van der Pol MA, Kok A, Bontje PM, Roemen GM, Beelen RH, et al. Differences between the CD34+ and CD34− blast compartments in apoptosis resistance in acute myeloid leukemia. Haematologica. 2003;88:497–508.PubMedGoogle Scholar
  51. 51.
    Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–60.PubMedCrossRefGoogle Scholar
  52. 52.
    Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 2009;458:780–3.PubMedCrossRefGoogle Scholar
  53. 53.
    Raguz S, Yague E. Resistance to chemotherapy: new treatments and novel insights into an old problem. Br J Cancer. 2008;99:387–91.PubMedCrossRefGoogle Scholar
  54. 54.
    Fuchs E, Segre JA. Stem cells: a new lease on life. Cell. 2000;100:143–55.PubMedCrossRefGoogle Scholar
  55. 55.
    Morrison SJ, Qian D, Jerebek L, Thiel BA, Park IK, Ford PS, et al. A genetic determinant that specifically regulates the frequency of hematopoietic stem cells. J Immunol. 2002;168:635–42.PubMedGoogle Scholar
  56. 56.
    Shackleton M. Normal stem cells and cancer stem cells: similar and different. Semin Cancer Biol. 2010;20:85–92.PubMedCrossRefGoogle Scholar
  57. 57.
    Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003;423:409–14.PubMedCrossRefGoogle Scholar
  58. 58.
    Knudson Jr AG, Strong LC, Anderson DE. Heredity and cancer in man. Prog Med Genet. 1973;9:113–58.PubMedGoogle Scholar
  59. 59.
    Jaiswal S, Traver D, Miyamoto T, Akashi K, Lagasse E, Weissman IL. Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemia. Proc Natl Acad Sci USA. 2003;100:10002–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Shiras A, Chettiar ST, Shepal V, Rajendran G, Prasad GR, Shastry P. Spontaneous transformation of human adult nontumourigenic stem cells to cancer stem cells is driven by genomic instability in a human model of glioblastoma. Stem Cells. 2007;25:1478–89.PubMedCrossRefGoogle Scholar
  61. 61.
    Molyneux G, Geyer FC, Magnay FA, McCarthy A, Kendrick H, Natrajan R, et al. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell. 2010;7:403–17.PubMedCrossRefGoogle Scholar
  62. 62.
    Persson AI, Petritsch C, Swartling FJ, Itsara M, Sim FJ, Auvergne R, et al. Non-stem cell origin for oligodendroglioma. Cancer Cell. 2010;18:669–82.PubMedCrossRefGoogle Scholar
  63. 63.
    Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, Weissman IL. Similar MLL-ssociated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev. 2003;17:3029–35.PubMedCrossRefGoogle Scholar
  64. 64.
    Sell S, Pierce G. Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab Invest. 1994;70:6–22.PubMedGoogle Scholar
  65. 65.
    Ratajczak MZ. Cancer stem cells-normal stem cells "Jedi" that went over to the "dark side". Folia Histochem Cytobiol. 2005;43:175–81.PubMedGoogle Scholar
  66. 66.
    Zhao RC, Zhu Y, Shi Y. New hope for cancer treatment: exploring the distinction between normal adult stem cells and cancer stem cells. Pharmacol Ther. 2008;119:74–82.PubMedCrossRefGoogle Scholar
  67. 67.
    Spandidos DA. Oncogenes and tumour suppressor genes as paradigms in oncogenesis. J BUON. 2007;12:S9–12.Google Scholar
  68. 68.
    Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature. 2006;441:475–82.PubMedCrossRefGoogle Scholar
  69. 69.
    He XC, Yin T, Grindley JC, Tian Q, Sato T, Tao WA, et al. PTEN-deficient intestinal stem cells initiate intestinal polyposis. Nat Genet. 2007;39:189–98.PubMedCrossRefGoogle Scholar
  70. 70.
    Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003;423:302–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Molofsky AV, He S, Bydon M, Morrison SJ, Pardal R. Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev. 2005;19:1432–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Gil J, Stembalska A, Pesz KA, Sasiadek MM. Cancer stem cells: the theory and perspectives in cancer therapy. J Appl Genet. 2008;49:193–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Kléber M, Sommer L. Wnt signaling and the regulation of stem cell function. Curr Opin Cell Biol. 2004;16:681–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature. 2005;14:843–50.CrossRefGoogle Scholar
  75. 75.
    Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P, et al. Cutaneous cancer stem cell maintenance is dependent on beta-catenin signaling. Nature. 2008;452:650–3.PubMedCrossRefGoogle Scholar
  76. 76.
    Yeung J, Esposito MT, Gandillet A, Zeisig BB, Griessinger E, Bonnet D, et al. β-Catenin mediates the establishment and drug resistance of MLL leukemic stem cells. Cancer Cell. 2010;18:606–18.PubMedCrossRefGoogle Scholar
  77. 77.
    Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 2001;15:3059–87.PubMedCrossRefGoogle Scholar
  78. 78.
    Pepinsky RB, Rayhorn P, Day ES, Dergay A, Williams KP, Galdes A, et al. Mapping sonic hedgehog–receptor interactions by steric interference. J Biol Chem. 2000;275(10):10995–1001.PubMedCrossRefGoogle Scholar
  79. 79.
    Murone M, Rosenthal A, de Sauvage FJ. Sonic hedgehog signaling by the patched-smoothened receptor complex. Curr Biol. 1999;9:76–84.PubMedCrossRefGoogle Scholar
  80. 80.
    Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DY, Reiter JF. Vertebrate Smoothened functions at the primary cilium. Nature. 2005;437:1018–21.PubMedCrossRefGoogle Scholar
  81. 81.
    Pasca di Magliano M, Hebrok M. Hedgehog signaling in cancer formation and maintenance. Nat Rev Cancer. 2003;3:903–11.PubMedCrossRefGoogle Scholar
  82. 82.
    Medina V, Calvo MB, Díaz-Prado S, Espada J. Hedgehog signalling as a target in cancer stem cells. Clin Transl Oncol. 2009;11:199–207.PubMedCrossRefGoogle Scholar
  83. 83.
    Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284:770–6.PubMedCrossRefGoogle Scholar
  84. 84.
    Bray S. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006;7:678–89.PubMedCrossRefGoogle Scholar
  85. 85.
    Katoh M, Katoh M. Notch signaling in gastrointestinal tract. Int J Oncol. 2007;30:247–51.PubMedGoogle Scholar
  86. 86.
    Fox V, Gokhale PJ, Walsh JR, Matin M, Jones M, Andrews PW. Cell-cell signaling through NOTCH regulates human embryonic stem cell proliferation. Stem Cells. 2008;26:715–23.PubMedCrossRefGoogle Scholar
  87. 87.
    Taipale J, Beachy PA. The Hedgehog and Wnt signalling pathways in cancer. Nature. 2001;411:349–54.PubMedCrossRefGoogle Scholar
  88. 88.
    Radtke F, Raj K. The role of Notch in tumourigenesis: oncogene or tumour suppressor? Nat Rev Cancer. 2003;3:756–67.PubMedCrossRefGoogle Scholar
  89. 89.
    Boulay JL, Miserez AR, Zweifel C, Sivasankaran B, Kana V, Ghaffari A, et al. Loss of NOTCH2 positively predicts survival in subgroups of human glial brain tumours. PLoS One. 2007;2:e576.PubMedCrossRefGoogle Scholar
  90. 90.
    Lee SY, Kumano K, Nakazaki K, Sanada M, Matsumoto A, Yamamoto G, et al. Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma. Cancer Sci. 2009;100:920–6.PubMedCrossRefGoogle Scholar
  91. 91.
    Lino MM, Merlo A, Boulay JL. Notch signaling in glioblastoma: a developmental drug target? BMC Med. 2010;8:72.PubMedCrossRefGoogle Scholar
  92. 92.
    Spangrude GJ, Heimfeld S, Weissman IL. Purification and characterization of mouse hematopoietic stem cells. Science. 1988;241:58–62.PubMedCrossRefGoogle Scholar
  93. 93.
    Bhatia M, Wang JC, Kapp U, Bonnet D, Dick JE. Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci USA. 1997;94:5320–5.PubMedCrossRefGoogle Scholar
  94. 94.
    Hogan CJ, Shpall EJ, Keller G. Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice. Proc Natl Acad Sci USA. 2002;99:413–8.PubMedCrossRefGoogle Scholar
  95. 95.
    Kimura T, Asada R, Wang J, Kimura T, Morioka M, Matsui K. Identification of long-term repopulating potential of human cord blood-derived CD34-flt3- severe combined immunodeficiency-repopulating cells by intra-bone marrow injection. Stem Cells. 2007;25:1348–55.PubMedCrossRefGoogle Scholar
  96. 96.
    Kitamura T, Matsuoka Y, Kimura T, Takahashi M, Nakamoto T, Yosuda K, et al. In vivo dynamic of human cord-blood derived CD34−SCID-repopulating cells using intra-bone marrow injection. Leukemia. 2010;24:162–8.CrossRefGoogle Scholar
  97. 97.
    Taussig DC, Miraki-Moud F, Anjos-Afonso F, Pearce DJ, Allen K, Ridler C, et al. Anti-CD38 antibody-mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells. Blood. 2008;112:568–75.PubMedCrossRefGoogle Scholar
  98. 98.
    Taussig DC, Vargaftig J, Miraki-Moud F, Griessinger E, Sharrock K, Luke T, et al. Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34(−) fraction. Blood. 2010;115:1976–84.PubMedCrossRefGoogle Scholar
  99. 99.
    Schatton T, Frank NY, Frank MH. Identification and targeting of cancer stem cells. Bioessays. 2009;31:1038–49.PubMedCrossRefGoogle Scholar
  100. 100.
    Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, et al. Identification and characterization of tumourigenic liver cancer stem/progenitor cells. Gastroenterology. 2007;132:2542–56.PubMedCrossRefGoogle Scholar
  101. 101.
    Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, et al. Identification and expansion of the tumourigenic lung cancer stem cell population. Cell Death Differ. 2008;15:504–14.PubMedCrossRefGoogle Scholar
  102. 102.
    Cui F, Wang J, Chen D, Chen YJ. CD133 is a temporary marker of cancer stem cells in small cell lung cancer, but not in non-small cell lung cancer. Oncol Rep. 2010. doi: 10.3892/or.2010.1115.Google Scholar
  103. 103.
    Chu P, Clanton DJ, Snipas TS, Lee J, Mitchell E, Nguyen M-L, et al. Characterization of a subpopulation of colon cancer cells with stem cell-like properties. Int J Cancer. 2009;124:1312–21.PubMedCrossRefGoogle Scholar
  104. 104.
    Shi MF, Jiao J, Lu WG, Ye F, Ma D, Dong QG, et al. Identification of cancer stem cell-like cells from human epithelial ovarian carcinoma cell line. Cell Mol Life Sci. 2010;67:3915–25.PubMedCrossRefGoogle Scholar
  105. 105.
    Baba T, Convery PA, Matsumura N, Whitaker RS, Kondoh E, Perry T, et al. Epigenetic regulation of CD133 and tumourigenicity of CD133C ovarian cancer cells. Oncogene. 2009;28:209–18.PubMedCrossRefGoogle Scholar
  106. 106.
    Dontu G, Al-Hajj M, Abdullah W, Clarke MF, Wicha MS. Stem cells in normal breast development and breast cancer. Cell Prolif. 2003;36:59–72.PubMedCrossRefGoogle Scholar
  107. 107.
    Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–67.PubMedCrossRefGoogle Scholar
  108. 108.
    Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, et al. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumourigenesis. Cancer Res. 2009;69:3382–9.PubMedCrossRefGoogle Scholar
  109. 109.
    Su Y, Qiu Q, Zhang X, Jiang Z, Leng Q, Liu Z, et al. Aldehyde dehydrogenase 1 A1-positive cell population is enriched in tumour-initiating cells and associated with progression of bladder cancer. Cancer Epidemiol Biomarkers Prev. 2010;19:327–37.PubMedCrossRefGoogle Scholar
  110. 110.
    Penumatsa K, Edassery SL, Barua A, Bradaric MJ, Luborsky JL. Differential expression of aldehyde dehydrogenase 1A1 (ALDH1) in normal ovary and serous ovarian tumours. J Ovarian Res. 2010;3:28.PubMedCrossRefGoogle Scholar
  111. 111.
    Beier D, Hau P, Proescholdt M, Lohmeier A, Wischhusen J, Oefner PJ, et al. CD133(+) and CD133(−) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res. 2007;67:4010–5.PubMedCrossRefGoogle Scholar
  112. 112.
    Joo KM, Kim SY, Jin X, Song SY, Kong DS, Lee JI, et al. Clinical and biological implications of CD133-positive and CD133-negative cells in glioblastomas. Lab Invest. 2008;88:808–15.PubMedCrossRefGoogle Scholar
  113. 113.
    Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, et al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133 metastatic colon cancer cells initiate tumours. J Clin Invest. 2008;118:2111–20.PubMedGoogle Scholar
  114. 114.
    Cho RW, Clarke MF. Recent advances in cancer stem cells. Curr Opin Genet Dev. 2008;18:48–53.PubMedCrossRefGoogle Scholar
  115. 115.
    Tan BT, Park CY, Ailles LE, Weissman IL. The cancer stem cell hypothesis: a work in progress. Lab Invest. 2006;86:1203–7.PubMedCrossRefGoogle Scholar
  116. 116.
    Huang Y, Anderle P, Bussey KJ, Barbacioru C, Shankavaram U, Dai Z, et al. Membrane transporters and channels: role of the transportome in cancer chemosensitivity and chemoresistance. Cancer Res. 2004;64:4294–301.PubMedCrossRefGoogle Scholar
  117. 117.
    Elliott A, Adams J, Al-Hajj M. The ABCs of cancer stem cell drug resistance. IDrugs. 2010;13:632–5.PubMedGoogle Scholar
  118. 118.
    Tan B, Piwnica-Worms D, Ratner L. Multidrug resistance transporters and modulation. Curr Opin Oncol. 2000;12:450–8.PubMedCrossRefGoogle Scholar
  119. 119.
    Tamura K, Aoyagi M, Wakimoto H, Ando N, Nariai T, Yamamoto M, et al. Accumulation of CD133-positive glioma cells after high-dose irradiation by Gamma Knife surgery plus external beam radiation. J Neurosurg. 2010;113:310–8.PubMedCrossRefGoogle Scholar
  120. 120.
    Facchino S, Abdouh M, Chatoo W, Bernier G. BMI1 confers radioresistance to normal and cancerous neural stem cells through recruitment of the DNA damage response machinery. J Neurosci. 2010;30:10096–111.PubMedCrossRefGoogle Scholar
  121. 121.
    Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 2004;73:39–85.PubMedCrossRefGoogle Scholar
  122. 122.
    Ropolo M, Daga A, Griffero F, Foresta M, Casartelli G, Zunino A, et al. Comparative analysis of DNA repair in stem and nonstem glioma cell cultures. Mol Cancer Res. 2009;7:383–92.PubMedCrossRefGoogle Scholar
  123. 123.
    Viale A, De Franco F, Orleth A, Cambiaghi V, Giuliani V, Bossi D, et al. Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells. Nature. 2009;457:51–6.PubMedCrossRefGoogle Scholar
  124. 124.
    Zhou BB, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature. 2000;408:433–9.PubMedCrossRefGoogle Scholar
  125. 125.
    Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009;8:579–91.PubMedCrossRefGoogle Scholar
  126. 126.
    Kai K, Arima Y, Kamiya T, Saya H. Breast cancer stem cells. Breast Cancer. 2010;17:80–5.PubMedCrossRefGoogle Scholar
  127. 127.
    Massard C, Deutsch E, Soria JC. Tumour stem cell-targeted treatment: elimination or differentiation. Ann Oncol. 2006;17:1620–4.PubMedCrossRefGoogle Scholar
  128. 128.
    Rajan P, Srinivasan R. Targeting cancer stem cells in cancer prevention and therapy. Stem Cell Rev. 2008;4:211–6.PubMedCrossRefGoogle Scholar
  129. 129.
    Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP. Cancer stem cells—old concepts, new insights. Cell Death Differ. 2008;15:947–58.PubMedCrossRefGoogle Scholar
  130. 130.
    Spira AI, Carducci MA. Differentiation therapy. Curr Opin Pharmacol. 2003;3:338–43.PubMedCrossRefGoogle Scholar
  131. 131.
    Campos B, Wan F, Farhadi M, Ernst A, Zeppernick F, Tagscherer KE, et al. Differentiation therapy exerts antitumour effects on stem-like glioma cells. Clin Cancer Res. 2010;16:2715–28.PubMedCrossRefGoogle Scholar
  132. 132.
    Ohno R, Asou N, Ohnishi K. Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate. Leukemia. 2003;17:1454–63.PubMedCrossRefGoogle Scholar
  133. 133.
    Clarke N, Germain P, Altucci L, Gronemeyer H. Retinoids: potential in cancer prevention and therapy. Expert Rev Mol Med. 2004;6:1–23.PubMedCrossRefGoogle Scholar
  134. 134.
    Taddei A, Roche D, Bickmore WA, Almouzni G. The effects of histone deacetylase inhibitors on heterochromatin: implications for anticancer therapy? EMBO Rep. 2005;6:520–4.PubMedCrossRefGoogle Scholar
  135. 135.
    Butler LM, Zhou X, Xu WS, Scher HI, Rifkind RA, Marks PA, et al. The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin. Proc Natl Acad Sci USA. 2002;99:11700–5.PubMedCrossRefGoogle Scholar
  136. 136.
    Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G, et al. Bone morpho-genetic proteins inhibit the tumourigenic potential of human brain tumour-initiating cells. Nature. 2006;444:761–5.PubMedCrossRefGoogle Scholar
  137. 137.
    Schatzlein AG. Delivering cancer stem cell therapies—a role for nanomedicines? Eur J Cancer. 2006;42:1309–15.PubMedCrossRefGoogle Scholar
  138. 138.
    Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138:645–59.PubMedCrossRefGoogle Scholar
  139. 139.
    Riccioni R, Dupuis ML, Bernabei M, Petrucci E, Pasquini L, Mariani G, et al. The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor. Blood Cells Mol Dis. 2010;45:86–92.PubMedCrossRefGoogle Scholar
  140. 140.
    Jodoin J, Demeule M, Beliveau R. Inhibition of the multidrug resistance P-glycoprotein activity by green tea polyphenols. Biochim Biophys Acta. 2002;1542:149–59.PubMedCrossRefGoogle Scholar
  141. 141.
    Harbottle A, Daly AK, Atherton K, Campbell FC. Role of glutathione S-transferase P1, P-glycoprotein and multidrug resistance associated protein 1 in acquired doxorubicin resistance. Int J Cancer. 2001;92:777–83.PubMedCrossRefGoogle Scholar
  142. 142.
    Verma SP, Goldin BR, Lin PS. The inhibition of the estrogenic effects of pesticides and environmental chemicals by curcumin and isoflavonoids. Environ Health Perspect. 1998;106:807–12.PubMedCrossRefGoogle Scholar
  143. 143.
    Behnam Rassouli F, Matin MM, Iranshahi M, Bahrami AR, Neshati V, Mollazadeha S, et al. Mogoltacin enhances vincristine cytotoxicity in human transitional cell carcinoma (TCC) cell line. Phytomedicine. 2009;16:181–7.PubMedCrossRefGoogle Scholar
  144. 144.
    Neshati V, Matin MM, Iranshahi M, Bahrami AR, Behravan J, Mollazadeh S, et al. Cytotoxicity of vincristine on the 5637 cell line is enhanced by combination with conferone. Z Naturforsch C. 2009;64:317–22.PubMedGoogle Scholar
  145. 145.
    Mollazadeh S, Matin MM, Iranshahi M, Bahrami AR, Neshati V, Behnam Rassouli F. The enhancement of vincristine cytotoxicity by combination with feselol. J Asian Nat Prod Res. 2010;12:569–75.PubMedCrossRefGoogle Scholar
  146. 146.
    Le Cesne A, Blay JY, Judson I, Van Oosterom A, Verweij J, Radford J, et al. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. J Clin Oncol. 2005;23:576–84.PubMedCrossRefGoogle Scholar
  147. 147.
    Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 2006;5:219–34.PubMedCrossRefGoogle Scholar
  148. 148.
    Guzman ML, Neering SJ, Upchurch D, Grimes B, Howard DS, Rizzieri DA, et al. Nuclear factor-κB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood. 2001;98:2301–7.PubMedCrossRefGoogle Scholar
  149. 149.
    Griessinger E, Imbert V, Lagadec P, Gonthier N, Dubruil P, Romanelli A, et al. AS602868, a dual inhibitor of IKK2 and FLT3 to target AML cells. Leukemia. 2007;21:877–85.PubMedGoogle Scholar
  150. 150.
    Fuchs O. Transcription factor NF-κB inhibitors as a single therapeutic agent or in combination with classical chemotherapeutic agents for the treatment of hematologic malignancies. Curr Mol Pharmacol. 2010;3:98–122.PubMedGoogle Scholar
  151. 151.
    Miletti-González KE, Chen S, Muthukumaran N, Saglimbeni GN, Wu X, Yang J, et al. The CD44 receptor interacts with P-glycoprotein to promote cell migration and invasion in cancer. Cancer Res. 2005;65:6660–7.PubMedCrossRefGoogle Scholar
  152. 152.
    Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006;12:1167–74.PubMedCrossRefGoogle Scholar
  153. 153.
    Testa U, Riccioni R, Militi S, Coccia E, Stellacci E, Samoggia P, et al. Elevated expression of IL-3Rα in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis. Blood. 2002;100:2980–8.PubMedCrossRefGoogle Scholar
  154. 154.
    Graf M, Hecht K, Reif S, Pelka-Fleischer R, Pfister K, Schmetzer H. Expression and prognostic value of hemopoietic cytokine receptors in acute myeloid leukemia (AML): implications for future therapeutical strategies. Eur J Haematol. 2004;72:89–106.PubMedCrossRefGoogle Scholar
  155. 155.
    van Rhenen A, Moshaver B, Kelder A, Feller N, Nieuwint AW, Zweegman S, et al. Aberrant marker expression patterns on the CD34+CD38−-stem cell compartment in acute myeloid leukemia allows to distinguish the malignant from the normal stem cell compartment both at diagnosis and in remission. Leukemia. 2007;21:1700–7.PubMedCrossRefGoogle Scholar
  156. 156.
    Jin L, Lee EM, Ramshaw HS, Busflield SJ, Peoppl AG, Wilkinson L, et al. Monoclonal antibody-mediated targeting of CD123, IL-3 receptor α chain, eliminates human acute myeloid leukemic stem cells. Cell Stem Cell. 2009;5:31–42.PubMedCrossRefGoogle Scholar
  157. 157.
    Grinstein E, Wernet P. Cellular signaling in normal and cancerous stem cells. Cell Signal. 2007;19:2428–33.PubMedCrossRefGoogle Scholar
  158. 158.
    Rajan P, Panchision DM, Newell LF, McKay RD. BMPs signal alternately through a SMAD or FRAP-STAT pathway to regulate fate choice in CNS stem cells. J Cell Biol. 2003;161:911–21.PubMedCrossRefGoogle Scholar
  159. 159.
    Cloughesy TF, Yoshimoto K, Nghiemphu P, Brown K, Dang J, Zhu S, et al. Antitumour activity of rapamycin in a phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med. 2008;5(1):e8.PubMedCrossRefGoogle Scholar
  160. 160.
    Cooper MK, Porter JA, Young KE, Beachy PA. Teratogen mediated inhibition of target tissue response to Shh signaling. Science. 1998;280:1603–7.PubMedCrossRefGoogle Scholar
  161. 161.
    Berman DM, Karhadkar SS, Hallahan AR, Pritchard JI, Eberhart CG, Watkins DN, et al. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science. 2002;297:1559–61.PubMedCrossRefGoogle Scholar
  162. 162.
    Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006;66:6063–71.PubMedCrossRefGoogle Scholar
  163. 163.
    Peacock CD, Wang Q, Gesell GS, Corcoran-Schwartz IM, Jones E, Kim J, et al. Hedgehog signaling maintains a tumour stem cell compartment in multiple myeloma. Proc Natl Acad Sci USA. 2007;104:4048–53.PubMedCrossRefGoogle Scholar
  164. 164.
    Byers S, Shah S. Vitamin D and the regulation of Wnt/beta-catenin signaling and innate immunity in colorectal cancer. Nutr Rev. 2007;65:S118–20.PubMedCrossRefGoogle Scholar
  165. 165.
    Shih Ie M, Wang TL. Notch signaling, gamma-secretase inhibitors, and cancer therapy. Cancer Res. 2007;67:1879–82.PubMedCrossRefGoogle Scholar
  166. 166.
    Harrison H, Farnie G, Howell SJ, Rock RE, Stylianou S, Brennan KR, et al. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res. 2010;70:709–18.PubMedCrossRefGoogle Scholar
  167. 167.
    McDermott SP, Wicha MS. Targeting breast cancer stem cells. Mol Oncol. 2010;4:404–19.PubMedCrossRefGoogle Scholar
  168. 168.
    Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 2004;24:2783–840.PubMedGoogle Scholar
  169. 169.
    Das DK, Maulik N. Resveratrol in cardioprotection: a therapeutic promise of alternative medicine. Mol Interv. 2006;6:36–47.PubMedCrossRefGoogle Scholar
  170. 170.
    Cecchinato V, Chiaramonte R, Nizzardo M, Cristofaro B, Basile A, Sherbet GV, et al. Resveratrol-induced apoptosis in human T-cell acute lymphoblastic leukaemia MOLT-4 cells. Biochem Pharmacol. 2007;74:1568–74.PubMedCrossRefGoogle Scholar
  171. 171.
    Saito Y, Kitamura H, Hijikata A, Tomizawa-Murasawa M, Tanaka S, Takagi S, et al. Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia stem cells. Sci Transl Med. 2010;2:17ra9.Google Scholar
  172. 172.
    Dubrovska A, Elliott J, Salamone RJ, Kim S, Aimone LJ, Walker JR, et al. Combination therapy targeting both tumour-initiating and differentiated cell populations in prostate carcinoma. Clin Cancer Res. 2010;16:5692–702.PubMedCrossRefGoogle Scholar
  173. 173.
    Qian Z, Fernald AA, Godley LA, Larson RA, Le Beau MM. Expression profiling of CD34+ haematopoietic stem/progenitor cells reveals distinct subtypes of therapy-related acute myeloid leukemia. Proc Natl Acad Sci USA. 2002;99:14925–30.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2011

Authors and Affiliations

  1. 1.Department of Biology, Faculty of ScienceFerdowsi University of MashhadMashhadIran
  2. 2.Cell and Molecular Research Group, Institute of BiotechnologyFerdowsi University of MashhadMashhadIran

Personalised recommendations