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Solid Tumor Stem Cells – Implications for Cancer Therapy

  • Chapter
Regulatory Networks in Stem Cells

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Cancer stem cells (CSC) that drive tumor initiation and growth through self-renewal and differentiation have been identified in cancers of the hematopoietic lineage and certain solid tumors. Recent findings point to a specific relationship of such tumorigenic minority populations to therapeutic resistance and neoplastic progression. Furthermore, initial proof-of-concept has been established that specific targeting of CSC for cell killing is sufficient to halt experimental tumor growth. These findings indicate that such novel strategies could be suited to improve conventional cytotoxic therapies, which are believed to spare refractory tumor initiators responsible for recurrence and metastasis. Here, we review the currently available scientific evidence in support of the CSC model of tumor development, and discuss the implications of this emerging concept for tumor biology and cancer therapy.

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References

  1. Nowell PC. The clonal evolution of tumor cell populations. Science. 1976;194(4260):23–8.

    PubMed  CAS  Google Scholar 

  2. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.

    PubMed  CAS  Google Scholar 

  3. Futreal PA, Coin L, Marshall M, et al. A census of human cancer genes. Nat Rev. 2004;4(3):177–83.

    CAS  Google Scholar 

  4. Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004;10(8):789–99.

    PubMed  CAS  Google Scholar 

  5. Bruce WR, Van Der Gaag H. A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature. 1963;199:79–80.

    PubMed  CAS  Google Scholar 

  6. Fidler IJ, Hart IR. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982;217(4564):998–1003.

    PubMed  CAS  Google Scholar 

  7. Hamburger AW, Salmon SE. Primary bioassay of human tumor stem cells. Science. 1977;197(4302):461–3.

    PubMed  CAS  Google Scholar 

  8. Brunschwig A, Southam CM, Levin AG. Host resistance to cancer. Clinical experiments by homotransplants, autotransplants and admixture of autologous leucocytes. Ann Surg. 1965;162(3): 416–25.

    PubMed  CAS  Google Scholar 

  9. Morrison SJ, Kimble J. Asymmetric and symmetric stem-cell divisions in development and cancer. Nature. 2006;441(7097):1068–74.

    PubMed  CAS  Google Scholar 

  10. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145–7.

    PubMed  CAS  Google Scholar 

  11. Fuchs E. Scratching the surface of skin development. Nature. 2007;445(7130):834–42.

    PubMed  CAS  Google Scholar 

  12. Toma JG, Akhavan M, Fernandes KJ, et al. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol. 2001;3(9):778–84.

    PubMed  CAS  Google Scholar 

  13. Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418(6893):41–9.

    PubMed  CAS  Google Scholar 

  14. Guan K, Nayernia K, Maier LS, et al. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature. 2006;440(7088):1199–203.

    PubMed  CAS  Google Scholar 

  15. Harrison DE, Lerner CP. Most primitive hematopoietic stem cells are stimulated to cycle rapidly after treatment with 5-fluorouracil. Blood 1991;78(5):1237–40.

    PubMed  CAS  Google Scholar 

  16. Peters R, Leyvraz S, Perey L. Apoptotic regulation in primitive hematopoietic precursors. Blood. 1998;92(6):2041–52.

    PubMed  CAS  Google Scholar 

  17. Zhou S, Schuetz JD, Bunting KD, 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. Nature Med. 2001;7(9):1028–34.

    PubMed  CAS  Google Scholar 

  18. Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183(4): 1797–806.

    PubMed  CAS  Google Scholar 

  19. Molofsky AV, Pardal R, Morrison SJ. Diverse mechanisms regulate stem cell self-renewal. Curr Opin Cell Biol. 2004;16(6): 700–7.

    PubMed  CAS  Google Scholar 

  20. Scadden DT. The stem-cell niche as an entity of action. Nature. 2006;441(7097):1075–9.

    PubMed  CAS  Google Scholar 

  21. Leong KG, Karsan A. Recent insights into the role of Notch signaling in tumorigenesis. Blood. 2006;107(6):2223–33.

    PubMed  CAS  Google Scholar 

  22. Taipale J, Beachy PA. The Hedgehog and Wnt signalling pathways in cancer. Nature. 2001;411(6835):349–54.

    PubMed  CAS  Google Scholar 

  23. Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature. 2005;434(7035):843–50.

    PubMed  CAS  Google Scholar 

  24. Hendrix MJ, Seftor EA, Hess AR, Seftor RE. Molecular plasticity of human melanoma cells. Oncogene. 2003;22(20):3070–5.

    PubMed  CAS  Google Scholar 

  25. Kennedy JA, Barabe F, Poeppl AG, Wang JC, Dick JE. Comment on “Tumor growth need not be driven by rare cancer stem cells”. Science. 2007;318(5857):1722; author reply

    PubMed  CAS  Google Scholar 

  26. Schatton T, Murphy GF, Frank NY, et al. Identification of cells initiating human melanomas. Nature. 2008;451(7176):345–9.

    PubMed  CAS  Google Scholar 

  27. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367(6464):645–8.

    PubMed  CAS  Google Scholar 

  28. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature. Med. 1997;3(7):730–7.

    PubMed  CAS  Google Scholar 

  29. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100(7):3983–8.

    PubMed  CAS  Google Scholar 

  30. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature. 2004;432(7015): 396–401.

    PubMed  CAS  Google Scholar 

  31. 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(7123):106–10.

    PubMed  Google Scholar 

  32. Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111–5.

    PubMed  CAS  Google Scholar 

  33. Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A. 2007;104(24):10158–63.

    PubMed  CAS  Google Scholar 

  34. Hermann PC, Huber SL, Herrler T, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007;1:313–23.

    PubMed  CAS  Google Scholar 

  35. Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67(3):1030–7.

    PubMed  CAS  Google Scholar 

  36. Prince ME, Sivanandan R, Kaczorowski A, et al. 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. 2007;104(3):973–8.

    PubMed  CAS  Google Scholar 

  37. Uchida N, Buck DW, He D, et al. Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci U S A. 2000;97(26):14720–5.

    PubMed  CAS  Google Scholar 

  38. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992;255(5052):1707–10.

    PubMed  CAS  Google Scholar 

  39. Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63(18): 5821–8.

    PubMed  CAS  Google Scholar 

  40. Hemmati HD, Nakano I, Lazareff JA, et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A. 2003;100(25):15178–83.

    PubMed  CAS  Google Scholar 

  41. Galli R, Binda E, Orfanelli U, et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 2004;64(19):7011–21.

    PubMed  CAS  Google Scholar 

  42. Taylor MD, Poppleton H, Fuller C, et al. Radial glia cells are candidate stem cells of ependymoma. Cancer Cell. 2005;8(4): 323–35.

    PubMed  CAS  Google Scholar 

  43. Weichert W, Knosel T, Bellach J, Dietel M, Kristiansen G. ALCAM/CD166 is overexpressed in colorectal carcinoma and correlates with shortened patient survival. J Clin Pathol. 2004;57(11):1160–4.

    PubMed  CAS  Google Scholar 

  44. van Kempen LC, van den Oord JJ, van Muijen GN, Weidle UH, Bloemers HP, Swart GW. Activated leukocyte cell adhesion molecule/CD166, a marker of tumor progression in primary malignant melanoma of the skin. Am J Pathol. 2000;156(3): 769–74.

    PubMed  Google Scholar 

  45. Frank NY, Margaryan A, Huang Y, et al. ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res. 2005;65(10):4320–33.

    PubMed  CAS  Google Scholar 

  46. Peled A, Petit I, Kollet O, et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science. 1999;283(5403):845–8.

    PubMed  CAS  Google Scholar 

  47. Muller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410(6824): 50–6.

    PubMed  CAS  Google Scholar 

  48. Chu PG, Weiss LM. Keratin expression in human tissues and neoplasms. Histopathology. 2002;40(5):403–39.

    PubMed  CAS  Google Scholar 

  49. Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature. 2003;425(6961):962–7.

    PubMed  CAS  Google Scholar 

  50. Park IK, Qian D, Kiel M, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003;423(6937):302–5.

    PubMed  CAS  Google Scholar 

  51. Lessard J, Sauvageau G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 2003;423(6937):255–60.

    PubMed  CAS  Google Scholar 

  52. Suryo Rahmanto Y, Dunn LL, Richardson DR. Identification of distinct changes in gene expression after modulation of melanoma tumor antigen p97 (melanotransferrin) in multiple models in vitro and in vivo. Carcinogenesis. 2007;28(10):2172–83.

    PubMed  CAS  Google Scholar 

  53. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65(23):10946–51.

    PubMed  CAS  Google Scholar 

  54. Patrawala L, Calhoun T, Schneider-Broussard R, et al. Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene. 2006;25(12):1696–708.

    PubMed  CAS  Google Scholar 

  55. Patrawala L, Calhoun-Davis T, Schneider-Broussard R, Tang DG. Hierarchical organization of prostate cancer cells in xenograft tumors: the CD44+alpha2beta1+ cell population is enriched in tumor-initiating cells. Cancer Res. 2007;67(14):6796–805.

    PubMed  CAS  Google Scholar 

  56. Gibbs CP, Kukekov VG, Reith JD, et al. Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia. 2005;7(11):967–76.

    PubMed  CAS  Google Scholar 

  57. Fang D, Nguyen TK, Leishear K, et al. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res. 2005;65(20):9328–37.

    PubMed  CAS  Google Scholar 

  58. Monzani E, Facchetti F, Galmozzi E, et al. Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. Eur J Cancer. 2007;43(5):935–46.

    PubMed  CAS  Google Scholar 

  59. Haraguchi N, Utsunomiya T, Inoue H, et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells. 2006;24(3):506–13.

    PubMed  CAS  Google Scholar 

  60. Hirschmann-Jax C, Foster AE, Wulf GG, et al. A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci U S A. 2004;101(39): 14228–33.

    PubMed  CAS  Google Scholar 

  61. Ho MM, Ng AV, Lam S, Hung JY. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 2007;67(10):4827–33.

    PubMed  CAS  Google Scholar 

  62. Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci U S A. 2004;101(3):781–6.

    PubMed  CAS  Google Scholar 

  63. Ma S, Chan KW, Hu L, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007;132(7):2542–56.

    PubMed  CAS  Google Scholar 

  64. Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic. Cancer Res. 2005;65(14): 6207–19.

    PubMed  CAS  Google Scholar 

  65. Chambers I, Colby D, Robertson M, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003;113(5):643–55.

    PubMed  CAS  Google Scholar 

  66. Mitsui K, Tokuzawa Y, Itoh H, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003;113(5):631–42.

    PubMed  CAS  Google Scholar 

  67. Klein WM, Wu BP, Zhao S, Wu H, Klein-Szanto AJ, Tahan SR. Increased expression of stem cell markers in malignant melanoma. Mod Pathol. 2007;20(1):102–7.

    PubMed  CAS  Google Scholar 

  68. Grichnik JM, Burch JA, Schulteis RD, et al. Melanoma, a tumor based on a mutant stem cell? J Invest Dermatol. 2006;126(1):142–53.

    PubMed  CAS  Google Scholar 

  69. Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nature Immunol. 2004;5(7):738–43.

    CAS  Google Scholar 

  70. Kim CF, Jackson EL, Woolfenden AE, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005;121(6):823–35.

    PubMed  CAS  Google Scholar 

  71. Kato Y, Iwama A, Tadokoro Y, et al. Selective activation of STAT5 unveils its role in stem cell self-renewal in normal and leukemic hematopoiesis. JExp Med. 2005;202(1):169–79.

    CAS  Google Scholar 

  72. Passegue E, Wagner EF, Weissman IL. JunB deficiency leads to a myeloproliferative disorder arising from hematopoietic stem cells. Cell. 2004;119(3):431–43.

    PubMed  CAS  Google Scholar 

  73. Krivtsov AV, Twomey D, Feng Z, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature. 2006;442(7104):818–22.

    PubMed  CAS  Google Scholar 

  74. Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, Weissman IL. Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev. 2003;17(24):3029–35.

    PubMed  CAS  Google Scholar 

  75. 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 leukemias. Proc Natl Acad Sci U S A. 2003;100(17):10002–7.

    PubMed  CAS  Google Scholar 

  76. Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Eng J Med. 2004;351(7):657–67.

    CAS  Google Scholar 

  77. Huntly BJ, Shigematsu H, Deguchi K, et al. MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell. 2004;6(6):587–96.

    PubMed  CAS  Google Scholar 

  78. Drynan LF, Pannell R, Forster A, et al. Mll fusions generated by Cre-loxP-mediated de novo translocations can induce lineage reassignment in tumorigenesis. EMBO J. 2005;24(17):3136–46.

    PubMed  CAS  Google Scholar 

  79. Fu SL, Huang YJ, Liang FP, et al. Malignant transformation of an epithelial cell by v-Src via tv-a-mediated retroviral infection: a new cell model for studying carcinogenesis. Biochem Biophys Res Commun 2005;338(2):830–8.

    PubMed  CAS  Google Scholar 

  80. Sun B, Chen M, Hawks CL, Pereira-Smith OM, Hornsby PJ. The minimal set of genetic alterations required for conversion of primary human fibroblasts to cancer cells in the subrenal capsule assay. Neoplasia. 2005;7(6):585–93.

    PubMed  CAS  Google Scholar 

  81. Houghton J, Stoicov C, Nomura S, et al. Gastric cancer originating from bone marrow-derived cells. Science. 2004;306(5701):1568–71.

    PubMed  CAS  Google Scholar 

  82. Schatton T, Frank MH. Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res. 2008;21(1):39–55.

    PubMed  CAS  Google Scholar 

  83. Liu R, Wang X, Chen GY, et al. The prognostic role of a gene signature. from tumorigenic breast-cancer cells. N Eng J Med. 2007;356(3):217–26.

    CAS  Google Scholar 

  84. Massague J. Sorting out breast-cancer gene signatures. N Eng J Med. 2007;356(3):294–7.

    CAS  Google Scholar 

  85. Shipitsin M, Campbell LL, Argani P, et al. Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007;11(3):259–73.

    PubMed  CAS  Google Scholar 

  86. Piccirillo SG, Reynolds BA, Zanetti N, et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature. 2006;444(7120):761–5.

    PubMed  CAS  Google Scholar 

  87. Frank NY, Kho AT, Schatton T, et al. Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin. J Cell Biol. 2006;175(1):99–110.

    PubMed  CAS  Google Scholar 

  88. Lim DA, Tramontin AD, Trevejo JM, Herrera DG, Garcia-Verdugo JM, Alvarez-Buylla A. Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron. 2000;28(3):713–26.

    PubMed  CAS  Google Scholar 

  89. Rothhammer T, Bataille F, Spruss T, Eissner G, Bosserhoff AK. Functional implication of BMP4 expression on angiogenesis in malignant melanoma. Oncogene. 2007;26(28):4158–70.

    PubMed  CAS  Google Scholar 

  90. Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol. 1999;155(3):739–52.

    PubMed  CAS  Google Scholar 

  91. Bar EE, Chaudhry A, Lin A, et al. Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma. Stem Cells. 2007;25(10):2524–33.

    PubMed  CAS  Google Scholar 

  92. Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol. 2007;17(2):165–72.

    PubMed  CAS  Google Scholar 

  93. Levy V, Lindon C, Harfe BD, Morgan BA. Distinct stem cell populations regenerate the follicle and interfollicular epidermis. Dev Cell. 2005;9(6):855–61.

    PubMed  CAS  Google Scholar 

  94. Liu S, Dontu G, Mantle ID, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006;66(12):6063–71.

    PubMed  CAS  Google Scholar 

  95. Peacock CD, Wang Q, Gesell GS, et al. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci U S A. 2007;104(10):4048–53.

    PubMed  CAS  Google Scholar 

  96. Reya T, Duncan AW, Ailles L, et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003;423(6938):409–14.

    PubMed  CAS  Google Scholar 

  97. Zhao C, Blum J, Chen A, et al. Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo. Cancer Cell. 2007;12(6):528–41.

    PubMed  CAS  Google Scholar 

  98. Zhu AJ, Watt FM. beta-catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion. Development. 1999;126(10): 2285–98.

    PubMed  CAS  Google Scholar 

  99. Fan X, Matsui W, Khaki L, et al. Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res. 2006;66(15):7445–52.

    PubMed  CAS  Google Scholar 

  100. Shen Q, Goderie SK, Jin L, et al. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science. 2004;304(5675):1338–40.

    PubMed  CAS  Google Scholar 

  101. Varnum-Finney B, Xu L, Brashem-Stein C, et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nature Med. 2000;6(11): 1278–81.

    PubMed  CAS  Google Scholar 

  102. Wang S, Garcia AJ, Wu M, Lawson DA, Witte ON, Wu H. Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation. Proc Natl Acad Sci U S A. 2006;103(5):1480–5.

    PubMed  CAS  Google Scholar 

  103. Yilmaz OH, Valdez R, Theisen BK, et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature. 2006;441(7092):475–82.

    PubMed  CAS  Google Scholar 

  104. Hay N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell. 2005;8(3):179–83.

    PubMed  CAS  Google Scholar 

  105. Kelly JW, Yeatman JM, Regalia C, Mason G, Henham AP. A high incidence of melanoma found in patients with multiple dysplastic naevi by photographic surveillance. Med J Aust. 1997;167(4):191–4.

    PubMed  CAS  Google Scholar 

  106. Kiaris H, Chatzistamou I, Trimis G, Frangou-Plemmenou M, Pafiti-Kondi A, Kalofoutis A. Evidence for nonautonomous effect of p53 tumor suppressor in carcinogenesis. Cancer Res. 2005;65(5):1627–30.

    PubMed  CAS  Google Scholar 

  107. Calabrese C, Poppleton H, Kocak M, et al. A perivascular niche for brain tumor stem cells. Cancer Cell. 2007;11(1):69–82.

    PubMed  CAS  Google Scholar 

  108. Bao S, Wu Q, Sathornsumetee S, et al. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res. 2006;66(16):7843–8.

    PubMed  CAS  Google Scholar 

  109. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nature Med. 2002;8(8):793–800.

    PubMed  CAS  Google Scholar 

  110. Frank MH, Sayegh MH. Immunomodulatory functions of mesenchymal stem cells. Lancet. 2004;363(9419):1411–2.

    PubMed  Google Scholar 

  111. Le Blanc K, Ringden O. Immunomodulation by mesenchymal stem cells and clinical experience. J intern Med. 2007;262(5):509–25.

    PubMed  CAS  Google Scholar 

  112. Kelly PN, Dakic A, Adams JM, Nutt SL, Strasser A. Tumor growth need not be driven by rare cancer stem cells. Science. 2007;317(5836):337.

    PubMed  CAS  Google Scholar 

  113. Albini A, Sporn MB. The tumour microenvironment as a target for chemoprevention. Nature Rev. 2007;7(2):139–47.

    CAS  Google Scholar 

  114. Frank NY, Pendse SS, Lapchak PH, et al. Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter. J Biol Chem. 2003;278(47): 47156–65.

    PubMed  CAS  Google Scholar 

  115. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nature Rev. 2002;2(1): 48–58.

    CAS  Google Scholar 

  116. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nature Rev. 2005;5(4):275–84.

    CAS  Google Scholar 

  117. de Grouw EP, Raaijmakers MH, Boezeman JB, et al. Preferential expression of a high number of ATP binding cassette transporters in both normal and leukemic CD34+CD38- cells. Leukemia. 2006;20(4):750–4.

    PubMed  Google Scholar 

  118. Costello RT, Mallet F, Gaugler B, et al. Human acute myeloid leukemia CD34+/CD38- progenitor cells have decreased sensitivity to chemotherapy and Fas-induced apoptosis, reduced immunogenicity, and impaired dendritic cell transformation capacities. Cancer Res. 2000;60(16):4403–11.

    PubMed  CAS  Google Scholar 

  119. Wulf GG, Wang RY, Kuehnle I, et al. A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. Blood. 2001;98(4):1166–73.

    PubMed  CAS  Google Scholar 

  120. Michor F, Hughes TP, Iwasa Y, et al. Dynamics of chronic myeloid leukaemia. Nature. 2005;435(7046):1267–70.

    PubMed  CAS  Google Scholar 

  121. Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444(7120):756–60.

    PubMed  CAS  Google Scholar 

  122. Yu F, Yao H, Zhu P, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007;131(6):1109–23.

    PubMed  CAS  Google Scholar 

  123. Guzman ML, Swiderski CF, Howard DS, et al. Preferential induction of apoptosis for primary human leukemic stem cells. Proc Natl Acad Sci U S A. 2002;99(25):16220–5.

    PubMed  CAS  Google Scholar 

  124. Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007;128(4):683–92.

    PubMed  CAS  Google Scholar 

  125. Eriksson M, Guse K, Bauerschmitz G, et al. Oncolytic adenoviruses kill breast cancer initiating CD44(+)CD24(-/Low) Cells. Mol Ther. 2007;15(12):2088–93.

    PubMed  CAS  Google Scholar 

  126. Jiang H, Gomez-Manzano C, Aoki H, et al. Examination of the therapeutic potential of Delta-24-RGD in brain tumor stem cells: role of autophagic cell death. J Natl Cancer Inst. 2007;99(18):1410–4.

    PubMed  CAS  Google Scholar 

  127. Boyer LA, Mathur D, Jaenisch R. Molecular control of pluripotency. Curr Opin Genet Dev. 2006;16(5):455–62.

    PubMed  CAS  Google Scholar 

  128. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3(6):415–28.

    PubMed  CAS  Google Scholar 

  129. Arce C, Perez-Plasencia C, Gonzalez-Fierro A, et al. A proof-of-principle study of epigenetic therapy added to neoadjuvant Doxorubicin cyclophosphamide for locally advanced breast cancer. PLoS ONE. 2006;1:e98.

    PubMed  Google Scholar 

  130. Fandy TE, Carraway H, Gore SD. DNA demethylating agents and histone deacetylase inhibitors in hematologic malignancies. Cancer J. 2007;13(1):40–8.

    PubMed  CAS  Google Scholar 

  131. Chapman EJ, Carrington JC. Specialization and evolution of endogenous small RNA pathways. Nat Rev Genet. 2007;8(11): 884–96.

    PubMed  CAS  Google Scholar 

  132. Kanazawa J, Ohta S, Shitara K, et al. Therapeutic potential of chimeric anti-(ganglioside GD3) antibody KM871: antitumor activity in xenograft model of melanoma and effector function analysis. Cancer Immunol Immunother. 2000;49(4–5): 253–8.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Transplantation Research Center, Children’s Hospital Boston & Brigham and Women’s Hospital, Harvard Medical School, 300 Longwood Avenue, 02115, Boston, MA, USA

    Tobias Schatton, Natasha Y. Frank & Markus H. Frank

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  1. Tobias Schatton
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  2. Natasha Y. Frank
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  3. Markus H. Frank
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Editors and Affiliations

  1. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Vinagolu K. Rajasekhar MSc, MPhil, PhD

  2. Invitrogen Corporation, Frederick, MD, USA

    Mohan C. Vemuri Ph.D.

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC, a part of Springer Science+Business Media, LLC

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Schatton, T., Frank, N.Y., Frank, M.H. (2009). Solid Tumor Stem Cells – Implications for Cancer Therapy. In: Rajasekhar, V.K., Vemuri, M.C. (eds) Regulatory Networks in Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-60327-227-8_40

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