Cancer Stem Cells in Solid Tumors

Chapter

Abstract

Confirmation and assessment of general applicability of cancer stem cell concept towards solid tumors greatly depends on development of reliable approaches to selectively identify populations of neoplastic cells carrying “stemness” features, such as extensive capacity for self-renewal and ability to undergo a range of differentiation events. This chapter describes such assays as sphere formation, side population isolation and cancer stem cell marker detection and addresses their potential pitfalls. Also discussed are the cell of origin of stem cells and remaining challenges in solid tumor stem cell research.

Keywords

Brain Breast Cell of origin Challenges Colon Head and neck Kidney Liver Ovary Pancreas Prostate Side population Skin Solid tumor Sphere assay Stem cell markers 

References

  1. 1.
    Sell S (2004) Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 51: 1–28PubMedCrossRefGoogle Scholar
  2. 2.
    Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194: 23–28PubMedCrossRefGoogle Scholar
  3. 3.
    Hill RP, Chambers AF, Ling V, et al. (1984) Dynamic heterogeneity: rapid generation of metastatic variants in mouse B16 melanoma cells. Science 224: 998–1001PubMedCrossRefGoogle Scholar
  4. 4.
    Reya T, Morrison SJ, Clarke MF, et al. (2001) Stem cells, cancer, and cancer stem cells. Nature 414: 105–111PubMedCrossRefGoogle Scholar
  5. 5.
    Overturf K, Al-Dhalimy M, Ou CN, et al. (1997) Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes. Am J Pathol 151: 1273–1280PubMedGoogle Scholar
  6. 6.
    Tsujimura A, Koikawa Y, Salm S, et al. (2002) Proximal location of mouse prostate epithelial stem cells: a model of prostatic homeostasis. J Cell Biol 157: 1257–1265PubMedCrossRefGoogle Scholar
  7. 7.
    Reynolds BA and Weiss S (1996) Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev Biol 175: 1–13PubMedCrossRefGoogle Scholar
  8. 8.
    Yuan X, Curtin J, Xiong Y, et al. (2004) Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23: 9392–9400PubMedCrossRefGoogle Scholar
  9. 9.
    Galli R, Binda E, Orfanelli U, et al. (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64: 7011–7021PubMedCrossRefGoogle Scholar
  10. 10.
    Singh SK, Clarke ID, Terasaki M, et al. (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63: 5821–5828PubMedGoogle Scholar
  11. 11.
    Lendahl U, Zimmerman LB and McKay RD (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60: 585–595PubMedCrossRefGoogle Scholar
  12. 12.
    Hemmati HD, Nakano I, Lazareff JA, et al. (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 100: 15178–15183PubMedCrossRefGoogle Scholar
  13. 13.
    Salmaggi A, Boiardi A, Gelati M, et al. (2006) Glioblastoma-derived tumorospheres identify a population of tumor stem-like cells with angiogenic potential and enhanced multidrug resistance phenotype. Glia 54: 850–860PubMedCrossRefGoogle Scholar
  14. 14.
    Ignatova TN, Kukekov VG, Laywell ED, et al. (2002) Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 39: 193–206PubMedCrossRefGoogle Scholar
  15. 15.
    Fang D, Nguyen TK, Leishear K, et al. (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65: 9328–9337PubMedCrossRefGoogle Scholar
  16. 16.
    Bapat SA, Mali AM, Koppikar CB, et al. (2005) Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res 65: 3025–3029PubMedGoogle Scholar
  17. 17.
    Singec I, Knoth R, Meyer RP, et al. (2006) Defining the actual sensitivity and specificity of the neurosphere assay in stem cell biology. Nat Methods 3: 801–806PubMedCrossRefGoogle Scholar
  18. 18.
    Robinson SN, Seina SM, Gohr JC, et al. (2005) Evidence for a qualitative hierarchy within the Hoechst-33342 'side population' (SP) of murine bone marrow cells. Bone Marrow Transplant 35: 807–818PubMedCrossRefGoogle Scholar
  19. 19.
    Zhou S, Schuetz JD, Bunting KD, et al. (2001) 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 7: 1028–1034PubMedCrossRefGoogle Scholar
  20. 20.
    Chiba T, Kita K, Zheng YW, et al. (2006) Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology (Baltimore, Md) 44: 240–251CrossRefGoogle Scholar
  21. 21.
    Hirschmann-Jax C, Foster AE, Wulf GG, et al. (2004) A distinct "side population" of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101: 14228–14233PubMedCrossRefGoogle Scholar
  22. 22.
    Zhou Z, Flesken-Nikitin A and Nikitin AY (2007) Prostate cancer associated with p53 and Rb deficiency arises from the stem/progenitor cell-enriched proximal region of prostatic ducts. Cancer Res 67: 5683–5690PubMedCrossRefGoogle Scholar
  23. 23.
    Christgen M, Ballmaier M, Bruchhardt H, et al. (2007) Identification of a distinct side population of cancer cells in the Cal-51 human breast carcinoma cell line. Mol Cell Biochem 306: 201–212PubMedCrossRefGoogle Scholar
  24. 24.
    Kondo T, Setoguchi T and Taga T (2004) Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA 101: 781–786PubMedCrossRefGoogle Scholar
  25. 25.
    Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, et al. (2006) Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci USA 103: 11154–11159PubMedCrossRefGoogle Scholar
  26. 26.
    Zhou J, Wulfkuhle J, Zhang H, et al. (2007) Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci USA 104: 16158–16163PubMedCrossRefGoogle Scholar
  27. 27.
    Shi GM, Xu Y, Fan J, et al. (2008) Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials. J Cancer Res Clin Oncol 134: 1155–1163PubMedCrossRefGoogle Scholar
  28. 28.
    Adamski D, Mayol JF, Platet N, et al. (2007) Effects of Hoechst 33342 on C2C12 and PC12 cell differentiation. FEBS Lett 581: 3076–3080PubMedCrossRefGoogle Scholar
  29. 29.
    Adhikari JS, Khaitan D, Arya MB, et al. (2005) Heterogeneity in the radiosensitizing effects of the DNA ligand hoechst-33342 in human tumor cell lines. J Cancer Res Ther 1: 151–161PubMedCrossRefGoogle Scholar
  30. 30.
    Miraglia S, Godfrey W, Yin AH, et al. (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 90: 5013–5021PubMedGoogle Scholar
  31. 31.
    Uchida N, Buck DW, He D, et al. (2000) Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA 97: 14720–14725PubMedCrossRefGoogle Scholar
  32. 32.
    Lee A, Kessler JD, Read TA, et al. (2005) Isolation of neural stem cells from the postnatal cerebellum. Nat Neurosci 8: 723–729PubMedCrossRefGoogle Scholar
  33. 33.
    Neuzil J, Stantic M, Zobalova R, et al. (2007) Tumour-initiating cells vs. cancer 'stem' cells and CD133: what’s in the name? Biochem Biophys Res Commun 355: 855–859PubMedCrossRefGoogle Scholar
  34. 34.
    Liu G, Yuan X, Zeng Z, et al. (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 5: 67PubMedCrossRefGoogle Scholar
  35. 35.
    Singh SK, Hawkins C, Clarke ID, et al. (2004) Identification of human brain tumour initiating cells. Nature 432: 396–401PubMedCrossRefGoogle Scholar
  36. 36.
    Jang T, Litofsky NS, Smith TW, et al. (2004) Aberrant nestin expression during ethylnitrosourea-(ENU)-induced neurocarcinogenesis. Neurobiol Dis 15: 544–552PubMedCrossRefGoogle Scholar
  37. 37.
    Okano H, Kawahara H, Toriya M, et al. (2005) Function of RNA-binding protein Musashi-1 in stem cells. Exp. Cell Res 306: 349–356CrossRefGoogle Scholar
  38. 38.
    Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100: 3983–3988PubMedCrossRefGoogle Scholar
  39. 39.
    Sneath RJ and Mangham DC (1998) The normal structure and function of CD44 and its role in neoplasia. Mol Pathol 51: 191–200PubMedCrossRefGoogle Scholar
  40. 40.
    Ponti D, Costa A, Zaffaroni N, et al. (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65: 5506–5511PubMedCrossRefGoogle Scholar
  41. 41.
    Wright MH, Calcagno AM, Salcido CD, et al. (2008) Brca1 breast tumors contain distinct CD44+/CD24– and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res 10: R10PubMedCrossRefGoogle Scholar
  42. 42.
    Sheridan C, Kishimoto H, Fuchs RK, et al. (2006) CD44+/CD24– breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res 8: R59PubMedCrossRefGoogle Scholar
  43. 43.
    Ginestier C, Hur MH, Charafe-Jauffret E, 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: 555–567PubMedCrossRefGoogle Scholar
  44. 44.
    Zhang M, Behbod F, Atkinson RL, et al. (2008) Identification of tumor-initiating cells in a p53-null mouse model of breast cancer. Cancer Res 68: 4674–4682PubMedCrossRefGoogle Scholar
  45. 45.
    Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445: 111–115PubMedCrossRefGoogle Scholar
  46. 46.
    O‘Brien CA, Pollett A, Gallinger S, et al. (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445: 106–110PubMedCrossRefGoogle Scholar
  47. 47.
    Moll R (1998) Cytokeratins as markers of differentiation in the diagnosis of epithelial tumors. Subcell Biochem 31: 205–262PubMedGoogle Scholar
  48. 48.
    Eckert RL and Welter JF (1996) Transcription factor regulation of epidermal keratinocyte gene expression. Mol Biol Rep 23: 59–70PubMedCrossRefGoogle Scholar
  49. 49.
    Prince ME, Sivanandan R, Kaczorowski A, 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 USA 104: 973–978PubMedCrossRefGoogle Scholar
  50. 50.
    Bussolati B, Bruno S, Grange C, et al. (2008) Identification of a tumor-initiating stem cell population in human renal carcinomas. Faseb J 22: 3696–3705PubMedCrossRefGoogle Scholar
  51. 51.
    Suetsugu A, Nagaki M, Aoki H, et al. (2006) Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun 351: 820–824PubMedCrossRefGoogle Scholar
  52. 52.
    Zhang S, Balch C, Chan MW, et al. (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68: 4311–4320PubMedCrossRefGoogle Scholar
  53. 53.
    Li C, Heidt DG, Dalerba P, et al. (2007) Identification of pancreatic cancer stem cells. Cancer Res 67: 1030–1037PubMedCrossRefGoogle Scholar
  54. 54.
    Hermann PC, Huber SL, Herrler T, et al. (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1: 313–323PubMedCrossRefGoogle Scholar
  55. 55.
    Richardson GD, Robson CN, Lang SH, et al. (2004) CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci 117: 3539–3545PubMedCrossRefGoogle Scholar
  56. 56.
    Collins AT, Berry PA, Hyde C, et al. (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65: 10946–10951PubMedCrossRefGoogle Scholar
  57. 57.
    Patrawala L, Calhoun T, Schneider-Broussard R, et al. (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25: 1696–1708PubMedCrossRefGoogle Scholar
  58. 58.
    Nikitin AY, Nafus MG, Zhou Z, et al. (2008) Prostate stem cells and cancer in animals. In: Bagley RG and Teicher BA (Eds.) Stem Cells and Cancer, 1st edn, Springer Science & Humana Press, Totowa, NJGoogle Scholar
  59. 59.
    Kath R, Jambrosic JA, Holland L, et al. (1991) Development of invasive and growth factor-independent cell variants from primary human melanomas. Cancer Res 51: 2205–2211PubMedGoogle Scholar
  60. 60.
    Reed JA, Finnerty B and Albino AP (1999) Divergent cellular differentiation pathways during the invasive stage of cutaneous malignant melanoma progression. Am J Pathol 155: 549–555PubMedCrossRefGoogle Scholar
  61. 61.
    Frank NY, Pendse SS, Lapchak PH, et al. (2003) Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter. J Biol Chem 278: 47156–47165PubMedCrossRefGoogle Scholar
  62. 62.
    Schatton T, Murphy GF, Frank NY, et al. (2008) Identification of cells initiating human melanomas. Nature 451: 345–349PubMedCrossRefGoogle Scholar
  63. 63.
    Malanchi I, Peinado H, Kassen D, et al. (2008) Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling. Nature 452: 650–653PubMedCrossRefGoogle Scholar
  64. 64.
    Morel AP, Lievre M, Thomas C, et al. (2008) Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS ONE 3: e2888PubMedCrossRefGoogle Scholar
  65. 65.
    Liu JC, Deng T, Lehal RS, et al. (2007) Identification of tumorsphere- and tumor-initiating cells in HER2/Neu-induced mammary tumors. Cancer Res 67: 8671–8681PubMedCrossRefGoogle Scholar
  66. 66.
    Zhou Z, Flesken-Nikitin A, Corney DC, et al. (2006) Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res 66: 7889–7898PubMedCrossRefGoogle Scholar
  67. 67.
    Nikitin AY, Matoso A and Roy-Burman P (2007) Prostate stem cells and cancer. Histol Histopathol 22: 1043–1049PubMedGoogle Scholar
  68. 68.
    Xin L, Lawson DA and Witte ON (2005) The Sca-1 cell surface marker enriches for a prostate-regenerating cell subpopulation that can initiate prostate tumorigenesis. Proc Natl Acad Sci USA 102: 6942–6947PubMedCrossRefGoogle Scholar
  69. 69.
    Wang S, Garcia AJ, Wu M, et al. (2006) Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation. Proc Natl Acad Sci USA 103: 1480–1485PubMedCrossRefGoogle Scholar
  70. 70.
    Alvarez-Buylla A, Seri B and Doetsch F (2002) Identification of neural stem cells in the adult vertebrate brain. Brain Res Bull 57: 751–758PubMedCrossRefGoogle Scholar
  71. 71.
    Recht L, Jang T, Savarese T, et al. (2003) Neural stem cells and neuro-oncology: quo vadis? J Cell Biochem 88: 11–19PubMedCrossRefGoogle Scholar
  72. 72.
    Rubinstein LJ, Herman MM and VanderBerg SR (1984) Differentiation and anaplasia in central neuroepithelial tumors. Progress in experimental tumor research. Fortschr Experimentellen Tumorforschung 27: 32–48Google Scholar
  73. 73.
    Sanai N, Tramontin AD, Quinones-Hinojosa A, et al. (2004) Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427: 740–744PubMedCrossRefGoogle Scholar
  74. 74.
    Danks RA, Orian JM, Gonzales MF, et al. (1995) Transformation of astrocytes in transgenic mice expressing SV40 T antigen under the transcriptional control of the glial fibrillary acidic protein promoter. Cancer Res 55: 4302–4310PubMedGoogle Scholar
  75. 75.
    Holland EC (2001) Gliomagenesis: genetic alterations and mouse models. Nat Rev Genet 2: 120–129PubMedCrossRefGoogle Scholar
  76. 76.
    Bachoo RM, Maher EA, Ligon KL, et al. (2002) Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer cell 1: 269–277PubMedCrossRefGoogle Scholar
  77. 77.
    Jensen NA, Pedersen KM, Lihme F, et al. (2003) Astroglial c-Myc overexpression predisposes mice to primary malignant gliomas. J Biol Chem 278: 8300–8308PubMedCrossRefGoogle Scholar
  78. 78.
    Rao G, Pedone CA, Coffin CM, et al. (2003) c-Myc enhances sonic hedgehog-induced medulloblastoma formation from nestin-expressing neural progenitors in mice. Neoplasia (New York, NY) 5: 198–204Google Scholar
  79. 79.
    Lantos PL and Pilkington GJ (1979) The development of experimental brain tumours. A sequential light and electron microscope study of the subependymal plate. I. Early lesions (abnormal cell clusters). Acta Neuropathol 45: 167–175PubMedCrossRefGoogle Scholar
  80. 80.
    Kang KS, Morita I, Cruz A, et al. (1997) Expression of estrogen receptors in a normal human breast epithelial cell type with luminal and stem cell characteristics and its neoplastically transformed cell lines. Carcinogenesis 18: 251–257PubMedCrossRefGoogle Scholar
  81. 81.
    Sun W, Kang KS, Morita I, et al. (1999) High susceptibility of a human breast epithelial cell type with stem cell characteristics to telomerase activation and immortalization. Cancer Res 59: 6118–6123PubMedGoogle Scholar
  82. 82.
    Tang Y, Kitisin K, Jogunoori W, et al. (2008) Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc Natl Acad Sci USA 105: 2445–2450PubMedCrossRefGoogle Scholar
  83. 83.
    Matoso A and Nikitin AY (2008) Cancer stem cells in solid tumors. In: Dittmar T and Zänker KS (Eds.) Cancer and Stem Cells, 1st edn, Nova Science, New YorkGoogle Scholar
  84. 84.
    Fortunel NO, Otu HH, Ng HH, et al. (2003) Comment on "'Stemness': transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature". Science 302: 393; author reply 393PubMedCrossRefGoogle Scholar
  85. 85.
    Ivanova NB, Dimos JT, Schaniel C, et al. (2002) A stem cell molecular signature. Science 298: 601–604PubMedCrossRefGoogle Scholar
  86. 86.
    Ramalho-Santos M, Yoon S, Matsuzaki Y, et al. (2002) "Stemness": transcriptional profiling of embryonic and adult stem cells. Science 298: 597–600PubMedCrossRefGoogle Scholar
  87. 87.
    Wong DJ, Liu H, Ridky TW, et al. (2008) Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2: 333–344PubMedCrossRefGoogle Scholar
  88. 88.
    Shipitsin M, Campbell LL, Argani P, et al. (2007) Molecular definition of breast tumor heterogeneity. Cancer cell 11: 259–273PubMedCrossRefGoogle Scholar
  89. 89.
    Owens DM and Watt FM (2003) Contribution of stem cells and differentiated cells to epidermal tumours. Nat Rev 3: 444–451CrossRefGoogle Scholar
  90. 90.
    Perez-Losada J and Balmain A (2003) Stem-cell hierarchy in skin cancer. Nat Rev 3: 434–443CrossRefGoogle Scholar
  91. 91.
    Welm BE, Tepera SB, Venezia T, et al. (2002) Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population. Dev Biol 245: 42–56PubMedCrossRefGoogle Scholar
  92. 92.
    Li Y, Welm B, Podsypanina K, et al. (2003) Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc Natl Acad Sci USA 100: 15853–15858PubMedCrossRefGoogle Scholar
  93. 93.
    Boulanger CA and Smith GH (2001) Reducing mammary cancer risk through premature stem cell senescence. Oncogene 20: 2264–2272PubMedCrossRefGoogle Scholar
  94. 94.
    Wechsler-Reya RJ (2003) Analysis of gene expression in the normal and malignant cerebellum. Recent Prog Horm Res 58: 227–248PubMedCrossRefGoogle Scholar
  95. 95.
    Weiss WA, Burns MJ, Hackett C, et al. (2003) Genetic determinants of malignancy in a mouse model for oligodendroglioma. Cancer Res 63: 1589–1595PubMedGoogle Scholar
  96. 96.
    Lin RC, Matesic DF, Marvin M, et al. (1995) Re-expression of the intermediate filament nestin in reactive astrocytes. Neurobiol Dis 2: 79–85PubMedCrossRefGoogle Scholar
  97. 97.
    Signoretti S, Waltregny D, Dilks J, et al. (2000) p63 is a prostate basal cell marker and is required for prostate development. Am J Pathol 157: 1769–1775PubMedCrossRefGoogle Scholar
  98. 98.
    Verhagen AP, Ramaekers FC, Aalders TW, et al. (1992) Colocalization of basal and luminal cell-type cytokeratins in human prostate cancer. Cancer Res 52: 6182–6187PubMedGoogle Scholar
  99. 99.
    Liao CP, Zhong C, Saribekyan G, et al. (2007) Mouse models of prostate adenocarcinoma with the capacity to monitor spontaneous carcinogenesis by bioluminescence or fluorescence. Cancer Res 67: 7525–7533PubMedCrossRefGoogle Scholar
  100. 100.
    Takahashi K and Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663–676PubMedCrossRefGoogle Scholar
  101. 101.
    Brawley C and Matunis E (2004) Regeneration of male germline stem cells by spermatogonial dedifferentiation in vivo. Science 304: 1331–1334PubMedCrossRefGoogle Scholar
  102. 102.
    Brockes JP and Kumar A (2002) Plasticity and reprogramming of differentiated cells in amphibian regeneration. Nat Rev Mol Cell Biol 3: 566–574PubMedCrossRefGoogle Scholar
  103. 103.
    Lo DC, Allen F and Brockes JP (1993) Reversal of muscle differentiation during urodele limb regeneration. Proc Natl Acad Sci USA 90: 7230–7234PubMedCrossRefGoogle Scholar
  104. 104.
    Briggs R and King TJ (1952) Transplantation of living nuclei from blastula cells into enucleated frogs' eggs. Proc Natl Acad Sci USA 38: 455–463PubMedCrossRefGoogle Scholar
  105. 105.
    Gurdon JB (1962) Adult frogs derived from the nuclei of single somatic cells. Dev Biol 4: 256–273PubMedCrossRefGoogle Scholar
  106. 106.
    Bao S, Wu Q, McLendon RE, et al. (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444: 756–760PubMedCrossRefGoogle Scholar
  107. 107.
    Jackson AL and Loeb LA (1998) The mutation rate and cancer. Genetics 148: 1483–1490PubMedGoogle Scholar
  108. 108.
    Burdall SE, Hanby AM, Lansdown MR, et al. (2003) Breast cancer cell lines: friend or foe? Breast Cancer Res 5: 89–95PubMedCrossRefGoogle Scholar
  109. 109.
    Yang ZJ and Wechsler-Reya RJ (2007) Hit 'em where they live: targeting the cancer stem cell niche. Cancer cell 11: 3–5PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Department of Biomedical SciencesCornell UniversityIthacaUSA

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