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The Idea and Evidence for the Tumor Stemness Switch

  • Chapter
Regulatory Networks in Stem Cells

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

Abstract

The maintenance of stemness of normal stem cell is a complex process, where transcription factors like Oct-4, Bmi-1, and signaling pathways such as Wnt/β-catenin play important roles. This molecular set of mechanisms not only expands the population (self-renewal) but also keeps stem cells in a state of “de-differentiation.” Thus, stemness and differentiation are mutually exclusive and tightly regulated, where the idea of variation of stemness over time has not been incorporated. However, unlike normal stem cell stemness, tumor stemness may not be tightly regulated, where complexity of tumor microenvironment, especially hypoxic stress may allow for variation in stemness.

In this review, we discuss the stem cell model of tumor growth and the emerging concept of tumor stemness. We also discuss our findings on the expansion of tumor stem cell–like side-population cells following hypoxic and drug-induced stress. We then propose a model of stemness switch, where quiescent TSCs (tumor stem cells) switch to a state of active and self-renewing TSC following stress.

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References

  1. Trott KR. Tumour stem cells: the biological concept and its application in cancer treatment. Radiother Oncol. 1994;30(1):1–5.

    Article  PubMed  CAS  Google Scholar 

  2. Buick RN, Till JE, McCulloch EA. Colony assay for proliferative blast cells circulating in myeloblastic leukaemia. Lancet. 1977;1(8016):862–3.

    Article  PubMed  CAS  Google Scholar 

  3. Iscove NN, Senn JS, Till JE, McCulloch EA. Colony formation by normal and leukemic human marrow cells in culture: effect of conditioned medium from human leukocytes. Blood. 1971;37(1):1–5.

    PubMed  CAS  Google Scholar 

  4. McCulloch EA, Buick RN, Till JE. Normal and leukemic hemopoiesis compared. Cancer. 1978;42(2 Suppl):845–53.

    Article  PubMed  CAS  Google Scholar 

  5. Till JE, Mak TW, Price GB, Senn JS, McCulloch EA. Cellular subclasses in human leukemic hemopoiesis. Hamatol Bluttransfus. 1976;19:33–45.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Fidler IJ, Kripke ML. Metastasis results from preexisting variant cells within a malignant tumor. Science. 1977;197(4306):893–5.

    Article  PubMed  CAS  Google Scholar 

  10. Fogh J, Fogh JM, Orfeo T. One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst. 1977;59(1):221–6.

    PubMed  CAS  Google Scholar 

  11. Giovanella BC, Stehlin JS, Jr., Williams LJ, Jr., Lee SS, Shepard RC. Heterotransplantation of human cancers into nude mice: a model system for human cancer chemotherapy. Cancer. 1978;42(5):2269–81.

    Article  PubMed  CAS  Google Scholar 

  12. Hajdu SI, Lemos LB, Kozakewich H, Helson L, Beattie EJ, Jr. Growth pattern and differentiation of human soft tissue sarcomas in nude mice. Cancer. 1981;47(1):90–8.

    Article  PubMed  CAS  Google Scholar 

  13. Hamburger A, Salmon SE. Primary bioassay of human myeloma stem cells. J Clin Invest. 1977;60(4):846–54.

    Article  PubMed  CAS  Google Scholar 

  14. Heppner GH. Tumor heterogeneity. Cancer Res. 1984;44(6):2259–65.

    PubMed  CAS  Google Scholar 

  15. Nowell PC. Mechanisms of tumor progression. Cancer Res. 1986;46(5):2203–7.

    PubMed  CAS  Google Scholar 

  16. Park CH, Bergsagel DE, McCulloch EA. Mouse myeloma tumor stem cells: a primary cell culture assay. J Natl Cancer Inst. 1971;46(2):411–22.

    PubMed  CAS  Google Scholar 

  17. Shimosato Y, Kameya T, Nagai K, et al. Transplantation of human tumors in nude mice. J Natl Cancer Inst. 1976;56(6):1251–60.

    PubMed  CAS  Google Scholar 

  18. Southam CM, Brunschwig A, Levin AG, Dizon QS. Effect of leukocytes on transplantability of human cancer. Cancer. 1966;19(11):1743–53.

    Article  PubMed  CAS  Google Scholar 

  19. Behbod F, Rosen JM. Will cancer stem cells provide new therapeutic targets? Carcinogenesis. 2005;26(4):703–11.

    Article  PubMed  CAS  Google Scholar 

  20. Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer. 2003;3(12): 895–902.

    Article  PubMed  CAS  Google Scholar 

  21. Dick JE. Breast cancer stem cells revealed. Proc Natl Acad Sci U S A. 2003;100(7):3547–9.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. 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.

    Article  PubMed  CAS  Google Scholar 

  24. Goodell MA. Multipotential stem cells and ‘side population’ cells. Cytotherapy. 2002;4(6):507–8.

    Article  PubMed  CAS  Google Scholar 

  25. 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.

    Article  PubMed  CAS  Google Scholar 

  26. Smalley MJ, Clarke RB. The mammary gland “side population”: a putative stem/progenitor cell marker? J Mammary Gland Biol Neoplasia. 2005;10(1):37–47.

    Article  PubMed  Google Scholar 

  27. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292(5819):154–6.

    Article  PubMed  CAS  Google Scholar 

  28. Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A. 1981;78(12):7634–8.

    Article  PubMed  CAS  Google Scholar 

  29. Bradley A, Evans M, Kaufman MH, Robertson E. Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature. 1984;309(5965):255–6.

    Article  PubMed  CAS  Google Scholar 

  30. Barrandon Y, Green H. Three clonal types of keratinocyte with different capacities for multiplication. Proc Natl Acad Sci U S A. 1987;84(8):2302–6.

    Article  PubMed  CAS  Google Scholar 

  31. Locke M, Heywood M, Fawell S, Mackenzie IC. Retention of intrinsic stem cell hierarchies in carcinoma-derived cell lines. Cancer Res. 2005;65(19):8944–50.

    Article  PubMed  CAS  Google Scholar 

  32. Ross RA, Spengler BA, Domenech C, Porubcin M, Rettig WJ, Biedler JL. Human neuroblastoma I-type cells are malignant neural crest stem cells. Cell Growth Differ. 1995;6(4): 449–56.

    PubMed  CAS  Google Scholar 

  33. Buick RN, MacKillop WJ. Measurement of self-renewal in culture of clonogenic cells from human ovarian carcinoma. Br J Cancer. 1981;44(3):349–55.

    Article  PubMed  CAS  Google Scholar 

  34. 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.

    Article  PubMed  CAS  Google Scholar 

  35. Tsuchida R, Das B, Yeger H, et al. Cisplatin treatment increases survival and expansion of a highly tumorigenic side-population fraction by upregulating VEGF/Flt1 autocrine signaling. Oncogene. 2008;27(28):3923–34.

    Article  PubMed  CAS  Google Scholar 

  36. Das B, Tsuchida R, Malkin D, Baruchel S, Yeger H. Hypoxia enhances tumor stemness by increasing the invasive and tumorigenic side-population fraction. Stem Cells. 2008;26(7):1818–30.

    Article  PubMed  Google Scholar 

  37. Das B, Tsuchida R, Baruchel S, Malkin D, Yeger H. The role of VEGF/Flt1 signaling in the maintenance of neuroblastoma side-population celll “stemness” during hypoxia. Advances in Neuroblastoma Research meeting, May 2006, Los Angeles.

    Google Scholar 

  38. Das B, Tsuchida R, Malkin D, Baruchel S, Yeger H. A stem cell model of tumor repair and regeneration. In: 99th Annual meeting of the American Association of Cancer Research; 2006; Washington DC: American Association of Cancer Research; 2006. p. 1567.

    Google Scholar 

  39. Hill RP. Identifying cancer stem cells in solid tumors: case not proven. Cancer Res. 2006;66(4):18911896.

    Article  Google Scholar 

  40. Mikkers H, Frisen J. Deconstructing stemness. EMBO J. 2005;24(15):2715–9.

    Article  PubMed  CAS  Google Scholar 

  41. Raaphorst FM. Self-renewal of hematopoietic and leukemic stem cells: a central role for the Polycomb-group gene Bmi-1. Trends Immunol. 2003;24(10):522–4.

    Article  PubMed  CAS  Google Scholar 

  42. Rao RR, Calhoun JD, Qin X, Rekaya R, Clark JK, Stice SL. Comparative transcriptional profiling of two human embryonic stem cell lines. Biotechnol Bioeng. 2004;88(3):273–86.

    Article  PubMed  CAS  Google Scholar 

  43. Lee J, Kim HK, Rho JY, Han YM, Kim J. The human OCT-4 isoforms differ in their ability to confer self-renewal. J Biol Chem. 2006;281(44):33554–65.

    Article  PubMed  CAS  Google Scholar 

  44. Jacobsen SE. Defining ‘stemness’: Notch and Wnt join forces? Nat Immunol. 2005;6(3):234–6.

    Article  PubMed  CAS  Google Scholar 

  45. Suda T, Arai F, Shimmura S. Regulation of stem cells in the niche. Cornea. 2005;24(8 Suppl):S12–7.

    Article  PubMed  Google Scholar 

  46. Sell S, Dunsford HA. Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma. Am J Pathol. 1989;134(6):1347–63.

    PubMed  CAS  Google Scholar 

  47. Sell S, Pierce GB. Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab Invest. 1994;70(1):6–22.

    PubMed  CAS  Google Scholar 

  48. Sell S. Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol. 2004;51(1):1–28.

    Article  PubMed  Google Scholar 

  49. Iwama A, Oguro H, Negishi M, Kato Y, Nakauchia H. Epigenetic regulation of hematopoietic stem cell self-renewal by polycomb group genes. Int J Hematol. 2005;81(4):294–300.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  51. Glinsky GV, Berezovska O, Glinskii AB. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest. 2005;115(6):1503–21.

    Article  PubMed  CAS  Google Scholar 

  52. Armstrong L, Hughes O, Yung S, et al. The role of PI3K/AKT, MAPK/ERK and NFkappabeta signalling in the maintenance of human embryonic stem cell pluripotency and viability highlighted by transcriptional profiling and functional analysis. Hum Mol Genet. 2006;15(11):1894–913.

    Article  PubMed  CAS  Google Scholar 

  53. Bhattacharya B, Miura T, Brandenberger R, et al. Gene expression in human embryonic stem cell lines: unique molecular signature. Blood. 2004;103(8):2956–64.

    Article  PubMed  CAS  Google Scholar 

  54. Covello KL, Kehler J, Yu H, et al. HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev. 2006;20(5):557–70.

    Article  PubMed  CAS  Google Scholar 

  55. Guo Y, Costa R, Ramsey H, et al. The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression. Proc Natl Acad Sci U S A. 2002;99(6):3663–7.

    Article  PubMed  CAS  Google Scholar 

  56. Hochedlinger K, Yamada Y, Beard C, Jaenisch R. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell. 2005;121(3):465–77.

    Article  PubMed  CAS  Google Scholar 

  57. Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat Rev Cancer. 2005;5(9):744–9.

    Article  PubMed  CAS  Google Scholar 

  58. Shimada H, Chatten J, Newton WA, Jr., et al. Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. J Natl Cancer Inst. 1984;73(2):405–16.

    PubMed  CAS  Google Scholar 

  59. Liu S, Dontu G, Wicha MS. Mammary stem cells, self-renewal pathways, and carcinogenesis. Breast Cancer Res. 2005;7(3): 86–95.

    Article  PubMed  CAS  Google Scholar 

  60. 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.

    Article  PubMed  CAS  Google Scholar 

  61. 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.

    Article  PubMed  CAS  Google Scholar 

  62. Wechsler-Reya R, Scott MP. The developmental biology of brain tumors. Annu Rev Neurosci. 2001;24:385–428.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  64. Wicha M, Liu S, Dontu G. Cancer stem cells: an old idea-a paradigm shift. Cancer Res. 2006;66:1883–90.

    Article  PubMed  CAS  Google Scholar 

  65. Heppner GH, Miller FR. The cellular basis of tumor progression. Int Rev Cytol. 1998;177:1–56.

    Article  PubMed  CAS  Google Scholar 

  66. Klein G. Foulds’ dangerous idea revisited: the multistep development of tumors 40 years later. Adv Cancer Res. 1998;72: 1–23.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  68. Mackillop W, Ciampi A, Till J, Buick R. A stem cell model of human tumor growth: implications for tumor cell clonogenic assay. J Natl Cancer Inst. 1983;70(1):9–16.

    PubMed  CAS  Google Scholar 

  69. Graeber G, Osmanian C, Jacks T, et al. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumors. Nature. 1996;379:88–90.

    Article  PubMed  CAS  Google Scholar 

  70. Harris A. Hypoxia- a key regulatory factor in tumor growth. Nat Rev Cancer. 2002;2:38.

    Article  PubMed  CAS  Google Scholar 

  71. Das B, Yeger H, Tsuchida R, et al. A hypoxia-driven vascular endothelial growth factor/Flt1 autocrine loop interacts with hypoxia-inducible factor-1alpha through mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 pathway in neuroblastoma. Cancer Res. 2005;65(16):7267–75.

    Article  PubMed  CAS  Google Scholar 

  72. Li L, Xie T. Stem cell niche: structure and function. Annu Rev Cell Dev Biol. 2005;21:605–31.

    Article  PubMed  CAS  Google Scholar 

  73. D’Ippolito G, Diabira S, Howard GA, Roos BA, Schiller PC. Low oxygen tension inhibits osteogenic differentiation and enhances stemness of human MIAMI cells. Bone 2006;39(3): 513–22.

    Article  PubMed  Google Scholar 

  74. Jiang YG, Luo Y, He DL, et al. Role of Wnt/beta-catenin signaling pathway in epithelial-mesenchymal transition of human prostate cancer induced by hypoxia-inducible factor-1alpha. Int J Urol. 2007;14(11):1034–9.

    Article  PubMed  CAS  Google Scholar 

  75. Rich JN. Cancer stem cells in radiation resistance. Cancer Res. 2007;67(19):8980–4.

    Article  PubMed  CAS  Google Scholar 

  76. Pear WS, Simon MC. Lasting longer without oxygen: the influence of hypoxia on Notch signaling. Cancer Cell. 2005;8(6): 435–7.

    Article  PubMed  CAS  Google Scholar 

  77. Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell. 2004;116(6):769–78.

    Article  PubMed  CAS  Google Scholar 

  78. Hattori K, Heissig B, Wu Y, et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med. 2002;8(8): 841–9.

    PubMed  CAS  Google Scholar 

  79. Brusselmans K, Bono F, Collen D, Herbert JM, Carmeliet P, Dewerchin M. A novel role for vascular endothelial growth factor as an autocrine survival factor for embryonic stem cells during hypoxia. J Biol Chem. 2005;280(5):3493–9.

    Article  PubMed  CAS  Google Scholar 

  80. Durand R. Intermittent blood flow in solid tumors-an under-appreciated source of “drug-resistance”. Cancer and Metastasis Rev. 2001;20:57–61.

    Article  CAS  Google Scholar 

  81. Das B, Tsuchida R, Baruchel S, Yeger H. Idea and evidence of “tumor stemness switch”. In: International workshop on cancer stem cell; 2005 November 10–12; Milan, Italy; 2005. p. 34.

    Google Scholar 

  82. Cook JA, Gius D, Wink DA, Krishna MC, Russo A, Mitchell JB. Oxidative stress, redox, and the tumor microenvironment. Semin Radiat Oncol. 2004;14(3):259–66.

    Article  PubMed  Google Scholar 

  83. Das B. The role of VEGF autocrine signaling in hypoxia and oxidative stress driven “stemness switch”: implications in solid tumor progression and metastasis. PhD thesis: Institute of Medical Sciences, University of Toronto; 2007.

    Google Scholar 

  84. Brawley C, Matunis E. Regeneration of male germline stem cells by spermatogonial dedifferentiation in vivo. Science. 2004;304(5675):1331–4.

    Article  PubMed  CAS  Google Scholar 

  85. Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2008;26(1):101–6.

    Article  PubMed  CAS  Google Scholar 

  86. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.

    Article  PubMed  CAS  Google Scholar 

  87. Wernig M, Meissner A, Foreman R, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 2007;448(7151):318–24.

    Article  PubMed  CAS  Google Scholar 

  88. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.

    Article  PubMed  CAS  Google Scholar 

  89. Jogi A, Ora I, Nilsson H, et al. Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype. Proc Natl Acad Sci U S A. 2002;99(10): 7021–6.

    Article  PubMed  CAS  Google Scholar 

  90. Hill RP, Milas L. The proportion of stem cells in murine tumors. Int J Radiat Oncol Biol Phys. 1989;16(2):513–8.

    Article  PubMed  CAS  Google Scholar 

  91. Dick JE. Normal and leukemic human stem cells assayed in SCID mice. Semin Immunol. 1996;8(4):197–206.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  93. 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.

    Article  PubMed  CAS  Google Scholar 

  94. Banerjee TK, Marx JJ, Jr., Spencer SK, Tiffany E. Human tumor stem cell clonogenic assay sensitivity in malignant tumors and clinical correlation. Wis Med J. 1982;81(12):19–22.

    PubMed  CAS  Google Scholar 

  95. 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.

    Article  PubMed  CAS  Google Scholar 

  96. Miller AC, Mog S, McKinney L, et al. Neoplastic transformation of human osteoblast cells to the tumorigenic phenotype by heavy metal-tungsten alloy particles: induction of genotoxic effects. Carcinogenesis. 2001;22(1):115–25.

    Article  PubMed  CAS  Google Scholar 

  97. Bissell MJ, Radisky D. Putting tumours in context. Nat Rev Cancer. 2001;1(1):46–54.

    Article  PubMed  CAS  Google Scholar 

  98. Tscharntke M, Pofahl R, Krieg T, Haase I. Ras-induced spreading and wound closure in human epidermal keratinocytes. FASEB J. 2005;19(13):1836–8.

    PubMed  CAS  Google Scholar 

  99. Pai R, Jones MK, Tomikawa M, Tarnawski AS. Activation of Raf-1 during experimental gastric ulcer healing is Ras-mediated and protein kinase C-independent. Am J Pathol. 1999;155(5): 1759–66.

    Article  PubMed  CAS  Google Scholar 

  100. Kim JJ, Tannock IF. Repopulation of cancer cells during therapy: an important cause of treatment failure. Nat Rev Cancer. 2005;5(7):516–25.

    Article  PubMed  CAS  Google Scholar 

  101. Fowler JF. Rapid repopulation in radiotherapy: a debate on mechanism. The phantom of tumor treatment–continually rapid proliferation unmasked. Radiother Oncol. 1991;22(3):156–8.

    Article  PubMed  CAS  Google Scholar 

  102. Cottler-Fox MH, Lapidot T, Petit I, et al. Stem cell mobilization. Hematol Am Soc Hematol Educ Prog. 2003:419–37.

    Google Scholar 

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Authors and Affiliations

  1. Stem Cell and Developmental Biology Program, The Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, Canada

    Bikul Das, Rika Tsuchida, Sylvain Baruchel, David Malkin & Herman Yeger

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  1. Bikul Das
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  2. Rika Tsuchida
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  3. Sylvain Baruchel
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  4. David Malkin
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  5. Herman Yeger
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Correspondence to Bikul Das .

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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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Das, B., Tsuchida, R., Baruchel, S., Malkin, D., Yeger, H. (2009). The Idea and Evidence for the Tumor Stemness Switch. 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_35

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