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Influence of the Embryonic Microenvironment on Tumor Progression

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Cancer Stem Cells in Solid Tumors

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

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Abstract

Recent advancements in stem cell biology have revealed remarkable plasticity in cell fate specification. For example, fully differentiated somatic cells can be reprogrammed to pluripotent stem cells following the expression of specific stem cell associated transcription factors. This extraordinary process of cellular reprogramming or dedifferentiation shares many similarities with tumor progression, such that cancer cells often acquire stem cell-like plasticity concomitant with metastatic disease. Evidence suggests that cancer cells co-opt stem cell associated signaling factors to sustain plasticity. However, in contrast to normal stem cells, which have a complement of inhibitors and activators of pluripotency, cancer cells lack this critical balance. Here, we describe stem cell associated proteins and microenvironments that sustain and promote cellular plasticity in embryonic and neoplastic populations. We also review evidence that embryonic microenvironments may be capitalized upon to rebalance cancer cells toward a benign well-differentiated phenotype.

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Abbreviations

ADAM:

Disintegrin and metalloproteinase

ALK:

Activin-like kinase receptor type I

ATP:

Adenosine triphosphate

BCR-ABL:

Breakpoint cluster region-abelson

CBF-1:

C-promoter binding factor 1

CD:

Cluster of differentiation

ChIP:

Chromatin immunoprecipitation

DAPT:

N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester

EGF-CFC:

Epidermal growth factor-cripto FRL1 cryptic

EPO:

Erythropoietin

FOXH1:

Forkhead box HI

Gdf-1:

Growth differentiation factor-1

GLUT:

Glucose transporters

GPI:

Glycosyl-phosphatidylinositol

Gsc:

Goosecoid

HIF:

Hypoxia-inducible factor

HPV:

Human papilloma virus

hESCs:

Human embryonic stem cells

INK4:

Inhibitor of cyclin-dependent kinase 4

iPSC:

Induced pluripotent stem cells

MAML:

Mastermind/Lag

NICD:

Notch intracellular domain

NOD/SCID:

Non-obese diabetic/Severe combined immune deficiency

PI3K:

Phosphoinositol-3-kinase

RB:

Retinoblastoma

siRNA:

Small interfering RNA

T-ALL:

T-acute lymphoblastic leukemia

VEGF:

Vascular endothelial growth factor

References

  1. Hendrix MJ, Seftor EA, Seftor RE, Kasemeier-Kulesa J, Kulesa PM, Postovit LM (2007l) Reprogramming metastatic tumour cells with embryonic microenvironments. Nat Rev Cancer 7:246–255

    Article  PubMed  CAS  Google Scholar 

  2. Visvader JE, Lindeman GJ (2006) Mammary stem cells and mammopoiesis. Cancer Res 66:9798–9801

    Article  PubMed  CAS  Google Scholar 

  3. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    Article  PubMed  CAS  Google Scholar 

  4. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  PubMed  CAS  Google Scholar 

  5. Utikal J, Polo JM, Stadtfeld M, Maherali N, Kulalert W, Walsh RM, Khalil A, Rheinwald JG, Hochedlinger K (2009) Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460:1145–1148

    Article  PubMed  CAS  Google Scholar 

  6. Yoshida Y, Takahashi K, Okita K, Ichisaka T, Yamanaka S (2009) Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell 5:237–241

    Article  PubMed  CAS  Google Scholar 

  7. Dumont N, Wilson MB, Crawford YG, Reynolds PA, Sigaroudinia M, Tlsty TD (2008) Sustained induction of epithelial to mesenchymal transition activates DNA methylation of genes silenced in basal-like breast cancers. Proc Natl Acad Sci USA 105:14867–14872

    Article  PubMed  CAS  Google Scholar 

  8. Reynolds PA, Sigaroudinia M, Zardo G, Wilson MB, Benton GM, Miller CJ, Hong C, Fridlyand J, Costello JF, Tlsty TD (2006) Tumor suppressor p16INK4A regulates polycomb-mediated DNA hypermethylation in human mammary epithelial cells. J Biol Chem 281:24790–24802

    Article  PubMed  CAS  Google Scholar 

  9. Schier AF (2003) Nodal signaling in vertebrate development. Annu Rev Cell Dev Biol 19:589–621

    Article  PubMed  CAS  Google Scholar 

  10. Topczewska JM, Postovit LM, Margaryan NV, Sam A, Hess AR, Wheaton WW, Nickoloff BJ, Topczewski J, Hendrix MJ (2006) Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressiveness. Nat Med 12:925–932

    Article  PubMed  CAS  Google Scholar 

  11. Schier AF (2009) Nodal morphogens. Cold Spring Harb Perspect Biol 1:a003459

    Article  PubMed  CAS  Google Scholar 

  12. Strizzi L, Postovit LM, Margaryan NV, Seftor EA, Abbott DE, Seftor RE, Salomon DS, Hendrix MJ (2008) Emerging roles of nodal and Cripto-1: from embryogenesis to breast cancer progression. Breast Dis 29:91–-103

    PubMed  Google Scholar 

  13. Minchiotti G (2005) Nodal-dependant Cripto signaling in ES cells: from stem cells to tumor biology. Oncogene 24:5668–5675

    Article  PubMed  CAS  Google Scholar 

  14. Constam DB (2009) Running the gauntlet: an overview of the modalities of travel employed by the putative morphogen Nodal. Curr Opin Genet Dev 19:302–307

    Article  PubMed  CAS  Google Scholar 

  15. Tabibzadeh S, Hemmati-Brivanlou A (2006) Lefty at the crossroads of “stemness” and differentiative events. Stem Cells 24:1998–2006

    Article  PubMed  CAS  Google Scholar 

  16. Ang SL, Constam DB (2004) A gene network establishing polarity in the early mouse embryo. Semin Cell Dev Biol 15:555–561

    Article  PubMed  CAS  Google Scholar 

  17. Beck S, Le Good JA, Guzman M, Ben HN, Roy K, Beermann F, Constam DB (2002) Extraembryonic proteases regulate Nodal signalling during gastrulation. Nat Cell Biol 4:981–985

    Article  PubMed  CAS  Google Scholar 

  18. Constam DB (2009) Riding shotgun: a dual role for the epidermal growth factor-Cripto/FRL-1/Cryptic protein Cripto in Nodal trafficking. Traffic 10:783–791

    Article  PubMed  CAS  Google Scholar 

  19. Zhou X, Sasaki H, Lowe L, Hogan BL, Kuehn MR (1993) Nodal is a novel TGF-beta-like gene expressed in the mouse node during gastrulation. Nature 361:543–547

    Article  PubMed  CAS  Google Scholar 

  20. Collignon J, Varlet I, Robertson EJ (1996) Relationship between asymmetric nodal expression and the direction of embryonic turning. Nature 381:155–158

    Article  PubMed  CAS  Google Scholar 

  21. Smith JC (1995) Mesoderm-inducing factors and mesodermal patterning. Curr Opin Cell Biol 7:856–861

    Article  PubMed  CAS  Google Scholar 

  22. Takaoka K, Yamamoto M, Shiratori H, Meno C, Rossant J, Saijoh Y, Hamada H (2006) The mouse embryo autonomously acquires anterior-posterior polarity at implantation. Dev Cell 10:451–459

    Article  PubMed  CAS  Google Scholar 

  23. Vallier L, Mendjan S, Brown S, Chng Z, Teo A, Smithers LE, Trotter MW, Cho CH, Martinez A, Rugg-Gunn P, Brons G, Pedersen RA (2009) Activin/Nodal signalling maintains pluripotency by controlling Nanog expression. Development 136:1339–1349

    Article  PubMed  CAS  Google Scholar 

  24. Smith JR, Vallier L, Lupo G, Alexander M, Harris WA, Pedersen RA (2008) Inhibition of Activin/Nodal signaling promotes specification of human embryonic stem cells into neuroectoderm. Dev Biol 313:107–117

    Article  PubMed  CAS  Google Scholar 

  25. Patani R, Compston A, Puddifoot CA, Wyllie DJ, Hardingham GE, Allen ND, Chandran S (2009) Activin/Nodal inhibition alone accelerates highly efficient neural conversion from human embryonic stem cells and imposes a caudal positional identity. PLoS One 4:e7327

    Article  PubMed  CAS  Google Scholar 

  26. Adkins HB, Bianco C, Schiffer SG, Rayhorn P, Zafari M, Cheung AE, Orozco O, Olson D, De LA, Chen LL, Miatkowski K, Benjamin C, Normanno N, Williams KP, Jarpe M, LePage D, Salomon D, Sanicola M (2003) Antibody blockade of the Cripto CFC domain suppresses tumor cell growth in vivo. J Clin Invest 112:575–587

    PubMed  CAS  Google Scholar 

  27. Lee CC, Jan HJ, Lai JH, Ma HI, Hueng DY, Gladys Lee YC, Cheng YY, Liu LW, Wei HW, Lee HM (2010) Nodal promotes growth and invasion in human gliomas. Oncogene 29:3110–3123

    Article  PubMed  CAS  Google Scholar 

  28. Yu L, Harms PW, Pouryazdanparast P, Kim DS, Ma L, Fullen DR (2010) Expression of the embryonic morphogen Nodal in cutaneous melanocytic lesions. Mod Pathol 23:1209–1214

    Article  PubMed  CAS  Google Scholar 

  29. Postovit LM, Margaryan NV, Seftor EA, Kirschmann DA, Lipavsky A, Wheaton WW, Abbott DE, Seftor RE, Hendrix MJ (2008) Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells. Proc Natl Acad Sci USA 105:4329–4334

    Article  PubMed  CAS  Google Scholar 

  30. Lawrence M. (2009) Crosstalk between developmental and tumour-specific signalling pathways: Kallikrein-related serine peptidases and Nodal in prostate cancer. PhD thesis, QIT, Brisbane, Australia

    Google Scholar 

  31. Papageorgiou I, Nicholls PK, Wang F, Lackmann M, Makanji Y, Salamonsen LA, Robertson DM, Harrison CA (2009) Expression of nodal signalling components in cycling human endometrium and in endometrial cancer. Reprod Biol Endocrinol 7:122

    Article  PubMed  CAS  Google Scholar 

  32. Meyer MJ, Fleming JM, Ali MA, Pesesky MW, Ginsburg E, Vonderhaar BK (2009) Dynamic regulation of CD24 and the invasive, CD44posCD24neg phenotype in breast cancer cell lines. Breast Cancer Res. 11:R82

    Article  PubMed  CAS  Google Scholar 

  33. Lai EC (2004) Notch signaling: control of cell communication and cell fate. Development 131:965–973

    Article  PubMed  CAS  Google Scholar 

  34. Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol 7:678–689

    Article  PubMed  CAS  Google Scholar 

  35. Nichols JT, Miyamoto A, Olsen SL, D’Souza B, Yao C, Weinmaster G (2007) DSL ligand endocytosis physically dissociates Notch1 heterodimers before activating proteolysis can occur. J Cell Biol 176:445–458

    Article  PubMed  CAS  Google Scholar 

  36. Fortini ME (2002) Gamma-secretase-mediated proteolysis in cell-surface-receptor signalling. Nat Rev Mol Cell Biol 3:673–684

    Article  PubMed  CAS  Google Scholar 

  37. Mumm JS, Kopan R (2000) Notch signaling: from the outside in. Dev Biol 228:151–165

    Article  PubMed  CAS  Google Scholar 

  38. Nam Y, Aster JC, Blacklow SC (2002) Notch signaling as a therapeutic target. Curr Opin Chem Biol 6:501–509

    Article  PubMed  CAS  Google Scholar 

  39. Miele L, Golde T, Osborne B (2006) Notch signaling in cancer. Curr Mol Med 6:905–918

    Article  PubMed  CAS  Google Scholar 

  40. Raya A, Kawakami Y, Rodriguez-Esteban C, Buscher D, Koth CM, Itoh T, Morita M, Raya RM, Dubova I, Bessa JG, de la Pompa JL, Belmonte JC (2003) Notch activity induces Nodal expression and mediates the establishment of left-right asymmetry in vertebrate embryos. Genes Dev 17:1213–1218

    Article  PubMed  CAS  Google Scholar 

  41. Krebs LT, Iwai N, Nonaka S, Welsh IC, Lan Y, Jiang R, Saijoh Y, O’Brien TP, Hamada H, Gridley T (2003) Notch signaling regulates left-right asymmetry determination by inducing Nodal expression. Genes Dev 17:1207–1212

    Article  PubMed  CAS  Google Scholar 

  42. Iso T, Kedes L, Hamamori Y (2003) HES and HERP families: multiple effectors of the Notch signaling pathway. J Cell Physiol 194:237–255

    Article  PubMed  CAS  Google Scholar 

  43. Lewis J (1996) Neurogenic genes and vertebrate neurogenesis. Curr Opin Neurobiol 6:3–10

    Article  PubMed  CAS  Google Scholar 

  44. Lewis J (1998) Notch signalling. A short cut to the nucleus. Nature 393:304–305

    Article  PubMed  CAS  Google Scholar 

  45. Chitnis A, Henrique D, Lewis J, Ish-Horowicz D, Kintner C (1995) Primary neurogenesis in Xenopus embryos regulated by a homologue of the Drosophila neurogenic gene Delta. Nature 375:761–766

    Article  PubMed  CAS  Google Scholar 

  46. Henrique D, Hirsinger E, Adam J, Le R, I, Pourquie O, Ish-Horowicz D, Lewis J (1997) Maintenance of neuroepithelial progenitor cells by Delta-Notch signalling in the embryonic chick retina. Curr Biol 7:661–670

    Article  PubMed  CAS  Google Scholar 

  47. Radtke F, Raj K (2003) The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nat Rev Cancer 3:756–767

    Article  PubMed  CAS  Google Scholar 

  48. Kimble J, Simpson P (1997) The LIN-12/Notch signaling pathway and its regulation. Annu Rev Cell Dev Biol 13:333–361

    Article  PubMed  CAS  Google Scholar 

  49. Artavanis-Tsakonas S, Matsuno K, Fortini ME (1995) Notch signaling. Science 268:225–232

    Article  PubMed  CAS  Google Scholar 

  50. Pear WS, Radtke F (2003) Notch signaling in lymphopoiesis. Semin Immunol 15:69–79

    Article  PubMed  CAS  Google Scholar 

  51. Milner LA, Bigas A, Kopan R, Brashem-Stein C, Bernstein ID, Martin DI (1996) Inhibition of granulocytic differentiation by mNotch1. Proc Natl Acad Sci USA 93:13014–13019

    Article  PubMed  CAS  Google Scholar 

  52. Milner LA, Bigas A (1999) Notch as a mediator of cell fate determination in hematopoiesis: evidence and speculation. Blood 93:2431–2448

    PubMed  CAS  Google Scholar 

  53. Roy M, Pear WS, Aster JC (2007) The multifaceted role of Notch in cancer. Curr Opin Genet Dev 17:52–59

    Article  PubMed  CAS  Google Scholar 

  54. Rangarajan A, Syal R, Selvarajah S, Chakrabarti O, Sarin A, Krishna S (2001) Activated Notch1 signaling cooperates with papillomavirus oncogenes in transformation and generates resistance to apoptosis on matrix withdrawal through PKB/Akt. Virology 286:23–30

    Article  PubMed  CAS  Google Scholar 

  55. Munger K, Basile JR, Duensing S, Eichten A, Gonzalez SL, Grace M, Zacny VL (2001) Biological activities and molecular targets of the human papillomavirus E7 oncoprotein. Oncogene 20:7888–7898

    Article  PubMed  CAS  Google Scholar 

  56. Helt AM, Funk JO, Galloway DA (2002) Inactivation of both the retinoblastoma tumor suppressor and p21 by the human papillomavirus type 16 E7 oncoprotein is necessary to inhibit cell cycle arrest in human epithelial cells. J Virol 76:10559–10568

    Article  PubMed  CAS  Google Scholar 

  57. Westbrook TF, Nguyen DX, Thrash BR, McCance DJ (2002) E7 abolishes raf-induced arrest via mislocalization of p21(Cip1). Mol Cell Biol 22:7041–7052

    Article  PubMed  CAS  Google Scholar 

  58. Axelson H, Fredlund E, Ovenberger M, Landberg G, Pahlman S (2005) Hypoxia-induced dedifferentiation of tumor cells--a mechanism behind heterogeneity and aggressiveness of solid tumors. Semin Cell Dev Biol 16:554–563

    Article  PubMed  CAS  Google Scholar 

  59. Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM, Wicha MS (2004) Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res 6:R605–R615

    Article  PubMed  CAS  Google Scholar 

  60. Hitoshi S, Alexson T, Tropepe V, Donoviel D, Elia AJ, Nye JS, Conlon RA, Mak TW, Bernstein A, van der KD (2002) Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells. Genes Dev 16:846–858

    Article  PubMed  CAS  Google Scholar 

  61. Hitoshi S, Seaberg RM, Koscik C, Alexson T, Kusunoki S, Kanazawa I, Tsuji S, van der KD (2004) Primitive neural stem cells from the mammalian epiblast differentiate to definitive neural stem cells under the control of Notch signaling. Genes Dev 18:1806–1811

    Article  PubMed  CAS  Google Scholar 

  62. Strizzi L, Hardy KM, Seftor EA, Costa FF, Kirschmann DA, Seftor RE, Postovit LM, Hendrix MJ (2009) Development and cancer: at the crossroads of Nodal and Notch signaling. Cancer Res 69:7131–7134

    Article  PubMed  CAS  Google Scholar 

  63. Abbott DE, Bailey CM, Postovit LM, Seftor EA, Margaryan NV, Hendrix MJ (2008) The epigenetic influence of tumor and embryonic microenvironments: How different are they? Cancer Microenvironment 1:13–21.

    Article  PubMed  CAS  Google Scholar 

  64. Weijzen S, Rizzo P, Braid M, Vaishnav R, Jonkheer SM, Zlobin A, Osborne BA, Gottipati S, Aster JC, Hahn WC, Rudolf M, Siziopikou K, Kast WM, Miele L (2002) Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med 8:979–986

    Article  PubMed  CAS  Google Scholar 

  65. Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, Lockwood G, Egan SE (2005) High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res 65:8530–8537

    Article  PubMed  CAS  Google Scholar 

  66. Santagata S, Demichelis F, Riva A, Varambally S, Hofer MD, Kutok JL, Kim R, Tang J, Montie JE, Chinnaiyan AM, Rubin MA, Aster JC (2004) JAGGED1 expression is associated with prostate cancer metastasis and recurrence. Cancer Res 64:6854–6857

    Article  PubMed  CAS  Google Scholar 

  67. Bismar TA, Demichelis F, Riva A, Kim R, Varambally S, He L, Kutok J, Aster JC, Tang J, Kuefer R, Hofer MD, Febbo PG, Chinnaiyan AM, Rubin MA (2006) Defining aggressive prostate cancer using a 12-gene model. Neoplasia 8:59–68

    Article  PubMed  CAS  Google Scholar 

  68. Pece S, Serresi M, Santolini E, Capra M, Hulleman E, Galimberti V, Zurrida S, Maisonneuve P, Viale G, Di Fiore PP (2004) Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. J Cell Biol 167:215–221

    Article  PubMed  CAS  Google Scholar 

  69. Stylianou S, Clarke RB, Brennan K (2006) Aberrant activation of notch signaling in human breast cancer. Cancer Res 66:1517–1525

    Article  PubMed  CAS  Google Scholar 

  70. Balint K, Xiao M, Pinnix CC, Soma A, Veres I, Juhasz I, Brown EJ, Capobianco AJ, Herlyn M, Liu ZJ (2005) Activation of Notch1 signaling is required for beta-catenin-mediated human primary melanoma progression. J Clin Invest 115:3166–3176

    Article  PubMed  CAS  Google Scholar 

  71. Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E, Trombetta ES, Wu T, Niinobe M, Yoshikawa K, Hannigan GE, Halaban R (2004) Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res 64:5270–5282

    Article  PubMed  CAS  Google Scholar 

  72. Liu ZJ, Xiao M, Balint K, Smalley KS, Brafford P, Qiu R, Pinnix CC, Li X, Herlyn M (2006) Notch1 signaling promotes primary melanoma progression by activating mitogen-activated protein kinase/phosphatidylinositol 3-kinase-Akt pathways and up-regulating N-cadherin expression. Cancer Res 66:4182–4190

    Article  PubMed  CAS  Google Scholar 

  73. O’Neill CF, Urs S, Cinelli C, Lincoln A, Nadeau RJ, Leon R, Toher J, Mouta-Bellum C, Friesel RE, Liaw L (2007) Notch2 signaling induces apoptosis and inhibits human MDA-MB-231 xenograft growth. Am J Pathol 171:1023–1036

    Article  PubMed  CAS  Google Scholar 

  74. Nicolas M, Wolfer A, Raj K, Kummer JA, Mill P, van NM, Hui CC, Clevers H, Dotto GP, Radtke F (2003) Notch1 functions as a tumor suppressor in mouse skin. Nat Genet 33:416-421

    Article  PubMed  CAS  Google Scholar 

  75. Dreesen O, Brivanlou AH (2007) Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev 3:7–17

    Article  PubMed  CAS  Google Scholar 

  76. Takeuchi JK, Lickert H, Bisgrove BW, Sun X, Yamamoto M, Chawengsaksophak K, Hamada H, Yost HJ, Rossant J, Bruneau BG (2007) Baf60c is a nuclear Notch signaling component required for the establishment of left-right asymmetry. Proc Natl Acad Sci USA 104:846–851

    Article  PubMed  CAS  Google Scholar 

  77. Postovit LM, Seftor EA, Seftor RE, Hendrix MJ (2007) Targeting Nodal in malignant melanoma cells. Expert Opin Ther Targets 11:497–505

    Article  PubMed  CAS  Google Scholar 

  78. Watanabe K, Nagaoka T, Lee JM, Bianco C, Gonzales M, Castro NP, Rangel MC, Sakamoto K, Sun Y, Callahan R, Salomon DS (2009) Enhancement of Notch receptor maturation and signaling sensitivity by Cripto-1. J Cell Biol 187:343–353

    Article  PubMed  CAS  Google Scholar 

  79. Watanabe K, Kondo K, Takeuchi N, Okano H, Yamasoba T (2007) Musashi-1 expression in postnatal mouse olfactory epithelium. Neuroreport 18:641–644

    Article  PubMed  CAS  Google Scholar 

  80. Lunt SJ, Chaudary N, Hill RP (2009) The tumor microenvironment and metastatic disease. Clin Exp Metastasis 26:19–34

    Article  PubMed  Google Scholar 

  81. Postovit LM, Sullivan R, Adams MA, Graham CH (2005) Nitric oxide signalling and cellular adaptations to changes in oxygenation. Toxicology 208:235–248

    Article  PubMed  CAS  Google Scholar 

  82. Nathan AT, Singer M (1999) The oxygen trail: tissue oxygenation. Br Med Bull 55:96–108

    Article  PubMed  CAS  Google Scholar 

  83. Birol G, Wang S, Budzynski E, Wangsa-Wirawan ND, Linsenmeier RA (2007) Oxygen distribution and consumption in the macaque retina. Am J Physiol Heart Circ Physiol 293:H1696–H1704

    Article  PubMed  CAS  Google Scholar 

  84. Thomlinson RH, Gray LH (1955) The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9:539–549

    Article  PubMed  CAS  Google Scholar 

  85. Franko AJ, Sutherland RM (1978) Rate of death of hypoxic cells in multicell spheroids. Radiat Res 76:561–572

    Article  PubMed  CAS  Google Scholar 

  86. Durand RE, Raleigh JA (1998) Identification of nonproliferating but viable hypoxic tumor cells in vivo. Cancer Res 58:3547–3550

    PubMed  CAS  Google Scholar 

  87. Bennewith KL, Durand RE (2004) Quantifying transient hypoxia in human tumor xenografts by flow cytometry. Cancer Res 64:6183–6189

    Article  PubMed  CAS  Google Scholar 

  88. Lanzen J, Braun RD, Klitzman B, Brizel D, Secomb TW, Dewhirst MW (2006) Direct demonstration of instabilities in oxygen concentrations within the extravascular compartment of an experimental tumor. Cancer Res 66:2219–2223

    Article  PubMed  CAS  Google Scholar 

  89. Brurberg KG, Graff BA, Olsen DR, Rofstad EK (2004) Tumor-line specific pO2 fluctuations in human melanoma xenografts. Int J Radiat Oncol Biol Phys 58:403–409

    Article  PubMed  CAS  Google Scholar 

  90. Vaupel P, Hockel M (2000) Blood supply, oxygenation status and metabolic micromilieu of breast cancers: characterization and therapeutic relevance. Int J Oncol 17:869–879

    PubMed  CAS  Google Scholar 

  91. Hochachka PW, Lutz PL (2001) Mechanism, origin, and evolution of anoxia tolerance in animals. Comp Biochem Physiol B Biochem Mol Biol 130:435–459

    Article  PubMed  CAS  Google Scholar 

  92. Le QT, Denko NC, Giaccia AJ (2004) Hypoxic gene expression and metastasis. Cancer Metastasis Rev 23:293–310

    Article  PubMed  CAS  Google Scholar 

  93. Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3:721–732

    Article  PubMed  CAS  Google Scholar 

  94. Keith B, Simon MC (2007) Hypoxia-inducible factors, stem cells, and cancer. Cell 129:465–472

    Article  PubMed  CAS  Google Scholar 

  95. Genbacev O, Zhou Y, Ludlow JW, Fisher SJ (1997) Regulation of human placental development by oxygen tension. Science 277:1669–1672

    Article  PubMed  CAS  Google Scholar 

  96. Jauniaux E, Watson A, Burton G (2001) Evaluation of respiratory gases and acid-base gradients in human fetal fluids and uteroplacental tissue between 7 and 16 weeks’ gestation. Am J Obstet Gynecol 184:998–1003

    Article  PubMed  CAS  Google Scholar 

  97. Cipolleschi MG, Dello SP, Olivotto M (1993) The role of hypoxia in the maintenance of hematopoietic stem cells. Blood 82:2031–2037

    PubMed  CAS  Google Scholar 

  98. Danet GH, Pan Y, Luongo JL, Bonnet DA, Simon MC (2003) Expansion of human SCID-repopulating cells under hypoxic conditions. J Clin Invest 112:126–135

    PubMed  CAS  Google Scholar 

  99. Morrison SJ, Csete M, Groves AK, Melega W, Wold B, Anderson DJ (2000) Culture in reduced levels of oxygen promotes clonogenic sympathoadrenal differentiation by isolated neural crest stem cells. J Neurosci 20:7370–7376

    PubMed  CAS  Google Scholar 

  100. Studer L, Csete M, Lee SH, Kabbani N, Walikonis J, Wold B, McKay R (2000) Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J Neurosci 20:7377–7383

    PubMed  CAS  Google Scholar 

  101. Ezashi T, Das P, Roberts RM (2005) Low O2 tensions and the prevention of differentiation of hES cells. Proc Natl Acad Sci USA 102:4783–4788

    Article  PubMed  CAS  Google Scholar 

  102. Soeda A, Park M, Lee D, Mintz A, Androutsellis-Theotokis A, McKay RD, Engh J, Iwama T, Kunisada T, Kassam AB, Pollack IF, Park DM (2009) Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha. Oncogene 28:3949–3959

    Article  PubMed  CAS  Google Scholar 

  103. Pietras A, Gisselsson D, Ora I, Noguera R, Beckman S, Navarro S, Pahlman S (2008) High levels of HIF-2alpha highlight an immature neural crest-like neuroblastoma cell cohort located in a perivascular niche. J Pathol 214:482–488

    Article  PubMed  CAS  Google Scholar 

  104. Forsyth NR, Kay A, Hampson K, Downing A, Talbot R, McWhir J (2008) Transcriptome alterations due to physiological normoxic (2% O2) culture of human embryonic stem cells. Regen Med 3:817–833

    Article  PubMed  CAS  Google Scholar 

  105. Covello KL, Kehler J, Yu H, Gordan JD, Arsham AM, Hu CJ, Labosky PA, Simon MC, Keith B (2006) HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev 20:557–570

    Article  PubMed  CAS  Google Scholar 

  106. Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK, Trosko JE (2005) Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 26:495–502

    Article  PubMed  CAS  Google Scholar 

  107. Gidekel S, Pizov G, Bergman Y, Pikarsky E (2003) Oct-3/4 is a dose-dependent oncogenic fate determinant. Cancer Cell 4:361–370

    Article  PubMed  CAS  Google Scholar 

  108. Eilers M, Eisenman RN (2008) Myc’s broad reach. Genes Dev 22:2755–2766

    Article  PubMed  CAS  Google Scholar 

  109. Koshiji M, Kageyama Y, Pete EA, Horikawa I, Barrett JC, Huang LE (2004) HIF-1alpha induces cell cycle arrest by functionally counteracting Myc. EMBO J 23:1949–1956

    Article  PubMed  CAS  Google Scholar 

  110. Gordan JD, Bertout JA, Hu CJ, Diehl JA, Simon MC (2007) HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell 11:335–347

    Article  PubMed  CAS  Google Scholar 

  111. Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, Plath K, Hochedlinger K (2007) Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1:55–70

    Article  PubMed  CAS  Google Scholar 

  112. Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, Ruas JL, Poellinger L, Lendahl U, Bondesson M (2005) Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell 9:617–628

    Article  PubMed  CAS  Google Scholar 

  113. Prasad SM, Czepiel M, Cetinkaya C, Smigielska K, Weli SC, Lysdahl H, Gabrielsen A, Petersen K, Ehlers N, Fink T, Minger SL, Zachar V (2009) Continuous hypoxic culturing maintains activation of Notch and allows long-term propagation of human embryonic stem cells without spontaneous differentiation. Cell Prolif 42:63–74

    Article  PubMed  CAS  Google Scholar 

  114. Taylor MJ, Postovit LM (2009)The role of oxygen as a regulator of Nodal expression in breast cancer. Proceedings of the 100th annual meeting of the American Association of Cancer Research, Denver, Colorado, USA

    Google Scholar 

  115. Gerschenson M, Graves K, Carson SD, Wells RS, Pierce GB (1986) Regulation of melanoma by the embryonic skin. Proc Natl Acad Sci USA 83:7307–7310

    Article  PubMed  CAS  Google Scholar 

  116. Cucina A, Biava PM, D’Anselmi F, Coluccia P, Conti F, di CR, Miccheli A, Frati L, Gulino A, Bizzarri M (2006) Zebrafish embryo proteins induce apoptosis in human colon cancer cells (Caco2). Apoptosis 11:1617–1628

    Article  PubMed  CAS  Google Scholar 

  117. Lee LM, Seftor EA, Bonde G, Cornell RA, Hendrix MJ (2005) The fate of human malignant melanoma cells transplanted into zebrafish embryos: assessment of migration and cell division in the absence of tumor formation. Dev Dyn 233:1560–1570

    Article  PubMed  CAS  Google Scholar 

  118. Dolberg DS, Bissell MJ (1984) Inability of Rous sarcoma virus to cause sarcomas in the avian embryo. Nature 309:552–556

    Article  PubMed  CAS  Google Scholar 

  119. Kulesa PM, Kasemeier JC, Teddy JM, Margaryan NV, Seftor EA, Seftor RE, Hendrix MJ (2006) Reprogramming Metastatic Melanoma Cells to Assume a Neural Crest-Like Phenotype in an Embryonic Microenvironment. Proc Natl Acad Sci USA 103:3752–3757

    Article  PubMed  CAS  Google Scholar 

  120. Postovit LM, Seftor EA, Seftor RE, Hendrix MJ (2006) A three-dimensional model to study the epigenetic effects induced by the microenvironment of human embryonic stem cells. Stem Cells 24:501–505

    Article  PubMed  CAS  Google Scholar 

  121. Giuffrida D, Rogers IM, Nagy A, Calogero AE, Brown TJ, Casper RF (2009) Human embryonic stem cells secrete soluble factors that inhibit cancer cell growth. Cell Prolif 42:788–798

    Article  PubMed  CAS  Google Scholar 

  122. Hughes CS, Postovit LM, Lajoie GA (2010) Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10:1886–1890

    Article  PubMed  CAS  Google Scholar 

  123. Mintz B, Illmensee K (1975) Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci USA 72:3585–3589

    Article  PubMed  CAS  Google Scholar 

  124. Hochedlinger K, Blelloch R, Brennan C, Yamada Y, Kim M, Chin L, Jaenisch R (2004) Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev 18:1875–1885

    Article  PubMed  CAS  Google Scholar 

  125. Carette JE, Pruszak J, Varadarajan M, Blomen VA, Gokhale S, Camargo FD, Wernig M, Jaenisch R, Brummelkamp TR (2010) Generation of iPSCs from cultured human malignant cells. Blood 115:4039–4042

    PubMed  CAS  Google Scholar 

  126. Miyoshi N, Ishii H, Nagai K, Hoshino H, Mimori K, Tanaka F, Nagano H, Sekimoto M, Doki Y, Mori M (2010) Defined factors induce reprogramming of gastrointestinal cancer cells. Proc Natl Acad Sci USA 107:40–45

    Article  PubMed  CAS  Google Scholar 

  127. Utikal J, Maherali N, Kulalert W, Hochedlinger K (2009) Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J Cell Sci 122:3502–3510

    Article  PubMed  CAS  Google Scholar 

  128. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA (2008) An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40:499–507

    Article  PubMed  CAS  Google Scholar 

  129. Bendall SC, Stewart MH, Menendez P, George D, Vijayaragavan K, Werbowetski-Ogilvie T, Ramos-Mejia V, Rouleau A, Yang J, Bosse M, Lajoie G, Bhatia M (2007) IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro. Nature 448:1015–1021

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anatomy & Cell Biology, University of Western Ontario, London, ON, Canada

    Daniela Quail, Meghan Taylor, Michael Jewer & Lynne-Marie Postovit

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  1. Daniela Quail
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  2. Meghan Taylor
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  3. Michael Jewer
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  4. Lynne-Marie Postovit
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Correspondence to Lynne-Marie Postovit .

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  1. Dept. Oncology & Anatomy & Cell Biology, University of Western Ontario, Commissioners Road East 790, London, N6A 4L6, Ontario, Canada

    Alison L. Allan

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Quail, D., Taylor, M., Jewer, M., Postovit, LM. (2011). Influence of the Embryonic Microenvironment on Tumor Progression. In: Allan, A. (eds) Cancer Stem Cells in Solid Tumors. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-61779-246-5_13

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