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Stem Cells in Colon Cancer

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Stem Cells in Cancer: Should We Believe or Not?

Abstract

Colorectal cancer (CRC) is still one of the most commonly diagnosed and lethal cancers worldwide. The classic model of CRC carcinogenesis involves a multistep process of oncogenes activation and inactivation of tumor suppressor genes. But the cell of origin and the type of cells that propagate the tumor after its initiation are still unknown.

The concept of Cancer Stem Cells (CSC) was first developed for hematologic malignancies and later applied to solid neoplasias. This model suggests that tumors are hierarchically organized and only CSCs possess the ability to initiate tumors and due to their resistance to conventional treatments, they are also responsible for tumor relapse. The problem lies still in their identification which remains controversial due to the lack of specific molecular markers.

Colon CSCs were originally identified through the expression of the CD133. However, it is not definitively proven that CD133 is a reliable marker of colon CSCs and other cell surface markers, such as CD44, CD166, Musashi-1, CD24 among others have also been suggested.

Moreover, there are several molecular pathways (Wnt or Notch) as well as the complex crosstalk network between microenvironment and CSCs which are relevant for CRC.

Therefore the design of CSC-targeted agents would enhance responsiveness to traditional treatments and eventually reduce local recurrence and metastasis.

This review will discuss the newly introduced CSC model in CRC, the identification markers and the pathways involved in the design of novel therapeutic approaches and also the limitations associated with this model.

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References

  1. Alison M, Islam S, Wright N (2010) Stem cells in cancer: instigators and propagators? J Cell Sci 123(14):2357–2368

    Article  PubMed  CAS  Google Scholar 

  2. Arends JW (2000) Molecular interactions in the Vogelstein model of colorectal carcinoma. J Pathol 190:412–416

    Article  PubMed  CAS  Google Scholar 

  3. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–1007

    Article  PubMed  CAS  Google Scholar 

  4. Batlle E, Henderson JT, Beghtel H, van den Born MM, Sancho E, Huls G, Meeldijk J, Robertson J, van de Wetering M, Pawson T, Clevers H (2002) Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 111:251–263

    Article  PubMed  CAS  Google Scholar 

  5. Bauer N, Fonseca AV, Florek M, Freund D, Jászai J, Bornhäuser M, Fargeas CA, Corbeil D (2008) New insights into the cell biology of hematopoietic progenitors by studying prominin-1 (CD133). Cells Tissues Organs 188:127–138

    Article  PubMed  CAS  Google Scholar 

  6. Benhaim L, Labonte M, Lenz Heinz J (2011) Chapter 8: What do we know about cancer stem cells? Utilizing colon cancer as an example. In: Cancer stem cells – the cutting edge. InTech, Rijeka/Croatia

    Google Scholar 

  7. Bjerknes M, Cheng H (1999) Clonal analysis of mouse intestinal epithelial progenitors. Gastroenterology 116:7–14

    Article  PubMed  CAS  Google Scholar 

  8. Bjerknes M, Cheng H (2005) Gastrointestinal stem cells. II. Intestinal stem cells. Am J Physiol Gastrointest Liver Physiol 289:G381–G387

    Article  PubMed  CAS  Google Scholar 

  9. Boman BM, Huang E (2008) Human colon cancer stem cells: a new paradigm in gastrointestinal oncology. J Clin Oncol 26:2828–2838

    Article  PubMed  Google Scholar 

  10. Bonnet D, Dick J (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737

    Article  PubMed  CAS  Google Scholar 

  11. Booth C, Potten CS (2000) Gut instincts: thoughts on intestinal epithelial stem cells. J Clin Invest 105:1493–1499

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Bourguignon LY, Peyrollier K, Xia W, Gilad E (2008) Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells. J Biol Chem 283(25):17635–17651

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  13. Bussolati B, Bruno S, Grange C, Buttiglieri S, Deregibus MC (2005) Isolation of renal progenitor cells from adult human kidney. Am J Pathol 166:545–555

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Campbell L, Polyak K (2007) Breast tumor heterogeneity: cancer stem cells or clonal evolution? Cell Cycle 6:2332–2338

    Article  PubMed  CAS  Google Scholar 

  15. Cheng H, Leblond CP (1974) Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. I. Columnar cell. Am J Anat 141:461–479

    Article  PubMed  CAS  Google Scholar 

  16. Cheng H, Leblond CP (1974) Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types. Am J Anat 141:537–561

    Article  PubMed  CAS  Google Scholar 

  17. Cheng H, Bjerknes M, Amar J (1984) Methods for the determination of epithelial cell kinetic parameters of human colonic epithelium isolated from surgical and biopsy specimens. Gastroenterology 86:78–85

    PubMed  CAS  Google Scholar 

  18. Cobaleda C, Cruz J, González-Sarmiento R, Sánchez-García I, Pérez-Losada J (2008) The emerging picture of human breast cancer as a stem cell-based disease. Stem Cell Rev 4:67–79

    Article  PubMed  Google Scholar 

  19. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951

    Article  PubMed  CAS  Google Scholar 

  20. Corbeil D, Roper K, Hellwig A, Tavian M, Miraglia S, Watt SM, Simmons PJ, Peault B, Buck DW, Huttner WB (2000) The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. J Biol Chem 275:5512–5520

    Article  PubMed  CAS  Google Scholar 

  21. Corbeil D, Roper K, Fargeas CA, Joester A, Huttner WB (2001) Prominin: a story of cholesterol, plasma membrane protrusions and human pathology. Traffic 2:82–91

    Article  PubMed  CAS  Google Scholar 

  22. Cotsarelis G, Sun TT, Lavker RM (1990) Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61:1329–1337

    Article  PubMed  CAS  Google Scholar 

  23. Croker AK, Goodale D, Chu J, Postenka C, Hedley BD, Hess DA, Allan AL (2009) High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med 13(8B):2236–2252

    Article  PubMed  Google Scholar 

  24. Crosnier C, Stamataki D, Lewis J (2006) Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Nat Rev Genet 7:349–359

    Article  PubMed  CAS  Google Scholar 

  25. Dalerba P, Cho RW, Clarke MF (2007) Cancer stem cells: models and concepts. Annu Rev Med 58:267–284

    Article  PubMed  CAS  Google Scholar 

  26. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A 104(24):10158–10163

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Davies EJ, Marsh V, Clarke AR (2011) Origin and maintenance of the intestinal cancer stem cell. Mol Carcinog 50:254–263

    Article  PubMed  CAS  Google Scholar 

  28. Deonarain MP, Kousparou CA, Epenetos AA (2009) Antibodies targeting cancer stem cells: a new paradigm in immunotherapy? MAbs 1(1):12–25

    Article  PubMed Central  PubMed  Google Scholar 

  29. Dhawan P, Ahmad R, Srivastava AS, Singh AB (2011) Cancer stem cells and colorectal cancer: an overview. Curr Top Med Chem 11:1592–1598

    Article  PubMed  CAS  Google Scholar 

  30. Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17:1253–1270

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  31. Du L, Wang H, He L, Zhang J, Ni B, Wang X, Jin H, Cahuzac N, Mehrpour M, Lu Y, Chen Q (2008) CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res 14(21):6751–6760

    Article  PubMed  CAS  Google Scholar 

  32. Fevr T, Robine S, Louvard D, Huelsken J (2007) Wnt/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Mol Cell Biol 27:7551–7559

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  33. Freeman HJ (2008) Crypt region localization of intestinal stem cells in adults. World J Gastroenterol 14(47):7160–7162

    Article  PubMed Central  PubMed  Google Scholar 

  34. Fujimoto K, Beauchamp RD, Whitehead RH (2002) Identification and isolation of candidate human colonic clonogenic cells based on cell surface integrin expression. Gastroenterology 123:1941–1948

    Article  PubMed  CAS  Google Scholar 

  35. Gatenby RA, Vincent TL (2003) An evolutionary model of carcinogenesis. Cancer Res 63:6212–6220

    PubMed  CAS  Google Scholar 

  36. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer C, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. Goldman JM, Green AR, Holyoake T, Jamieson C, Mesa R, Mughal T, Pellicano F, Perrotti D, Skoda R, Vannucchi AM (2009). Chronic myeloproliferative diseases with and without the Ph chromosome: some unresolved issues. Leukemia 23:1708–1715

    Google Scholar 

  38. Grimm M, Kim M, Rosenwald A, Heemann U, Germer CT, Waaga-Gasser AM, Gasser M (2010) Toll-like receptor (TLR) 7 and TLR8 expression on CD133+ cells in colorectal cancer points to a specific role for inflammation-induced TLRs in tumourigenesis and tumour progression. Eur J Cancer 46(15):2849–2857

    Article  PubMed  CAS  Google Scholar 

  39. Haegebarth A, Clevers H (2009) Wnt signaling, Lgr5, and stem cells in the intestine and skin. Am J Pathol 174:715–721

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  40. Haraguchi N, Ohkuma M, Sakashita H, Matsuzaki S, Tanaka F, Mimori K, Kamohara Y, Inoue H, Mori M (2008) CD133 + CD44+ population efficiently enriches colon cancer initiating cells. Ann Surg Oncol 15(10):2927–2933

    Article  PubMed  Google Scholar 

  41. Horst D, Kriegl L, Engel J, Kirchner T, Jung A (2008) CD133 expression is an independent prognostic marker for low survival in colorectal cancer. Br J Cancer 99:1285–1289

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  42. Horst D, Kriegl L, Engel J, Jung A, Kirchner T (2009) CD133 and nuclear beta-catenin: the marker combination to detect high risk cases of low stage colorectal cancer. Eur J Cancer 45:2034–2040

    Article  PubMed  CAS  Google Scholar 

  43. Horst D, Scheel SK, Liebmann S, Neumann J, Maatz S, Kirchner T, Jung A (2009) The cancer stem cell marker CD133 has high prognostic impact but unknown functional relevance for the metastasis of human colon cancer. J Pathol 219(4):427–434

    Article  PubMed  CAS  Google Scholar 

  44. Huang EH, Wicha MS (2008) Colon cancer stem cells: implications for prevention and therapy. Trends Mol Med 14:503–509

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, Fields JZ, Wicha MS, Boman BM (2009) Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res 69:3382–3389

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  46. Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, Hild M, Shi X, Wilson CJ, Mickanin C, Myer V, Fazal A, Tomlinson R, Serluca F, Shao W, Cheng H, Shultz M, Rau C, Schirle M, Schlegl J, Ghidelli S, Fawell S, Lu C, Curtis D, Kirschner MW, Lengauer C, Finan PM, Tallarico JA, Bouwmeester T, Porter JA, Bauer A, Cong F (2009) Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461(7264):614–620

    Article  PubMed  CAS  Google Scholar 

  47. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  48. Kakarala M, Wicha M (2008) Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol 26:2813–2820

    Article  PubMed Central  PubMed  Google Scholar 

  49. Kiel MJ, He S, Ashkenazi R, Gentry SN, Teta M, Kushner JA, Jackson TL, Morrison SJ (2007) Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature 449:238–242

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  50. Kim SJ, Cheung S, Hellerstein MK (2004) Isolation of nuclei from label-retaining cells an measurement of their turnover rates in rat colon. Am J Physiol Cell Physiol 286:C1464–C1473

    Google Scholar 

  51. Kosinski C, Li VS, Chan AS, Zhang J, Ho C, Tsui WY, Chan TL, Mifflin RC, Powell DW, Yuen ST, Leung SY, Chen X (2007) Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc Natl Acad Sci U S A 104:15418–15423

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  52. Lampropoulos P, Zizi-Sermpetzoglou A, Rizos S, Kostakis A, Nikiteas N, Papavassiliou AG (2012) TGF-beta signalling in colon carcinogenesis. Cancer Lett 314:1–7

    Article  PubMed  CAS  Google Scholar 

  53. Lipkin M, Bell B, Sherlock P (1963) Cell proliferation kinetics in the gastrointestinal tract of man. I cell renewal in colon and rectum. J Clin Invest 42:767–776

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  54. Lopez-Garcia C, Klein AM, Simons BD, Winton DJ (2010) Intestinal stem cell replacement follows a pattern of neutral drift. Science 330:822–825

    Article  PubMed  CAS  Google Scholar 

  55. May R, Riehl TE, Hunt C, Sureban SM, Anant S, Houchen CW (2008) Identification of a novel putative gastrointestinal stem cell and adenoma stem cell marker, doublecortin and CaM kinase-like-1, following radiation injury and in adenomatous polyposis coli/multiple intestinal neoplasia mice. Stem Cells 26:630–637

    Article  PubMed  Google Scholar 

  56. Markowitz SD, Bertagnolli MM (2009) Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med 361:2449–2460

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  57. Maw MA, Corbeil D, Koch J, Hellwig A, Wilson-Wheeler JC, Bridges RJ, Kumaramanickavel G, John S, Nancarrow D, Roeper K, Weigmann A, Huttner WB, Denton MJ (2000) A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration. Hum Mol Genet 9:27–34

    Article  PubMed  CAS  Google Scholar 

  58. Medema JP, Vermeulen L (2011) Microenvironmental regulation of stem cells in intestinal homeostasis and cancer. Nature 474:318–326

    Article  PubMed  CAS  Google Scholar 

  59. Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, Bray RA, Waller EK, Buck DW (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 90:5013–5021

    PubMed  CAS  Google Scholar 

  60. Nakamura S, Kino I (1984) Morphogenesis of minute adenomas in familial polyposis coli. J Natl Cancer Inst 73:41–49

    PubMed  CAS  Google Scholar 

  61. Nakamura M, Okano H, Blendy JA, Montell C (1994) Musashi, a neural RNA-binding protein required for Drosophila adult external sensory organ development. Neuron 13:67–81

    Article  PubMed  CAS  Google Scholar 

  62. Navarro-Alvarez N, Kondo E, Kawamoto H, Hassan W, Yuasa T, Kubota Y, Seita M, Nakahara H, Hayashi T, Nishikawa Y, Hassan RA, Javed SM, Noguchi H, Matsumoto S, Nakaji S, Tanaka N, Kobayashi N, Soto-Gutierrez A (2010) Isolation and propagation of a human CD133(-) colon tumor-derived cell line with tumorigenic and angiogenic properties. Cell Transplant 19(6):865–877

    Article  PubMed Central  PubMed  Google Scholar 

  63. Nishimura S, Wakabayashi N, Toyoda K, Kashima K, Mitsufuji S (2003) Expression of Musashi-1 in human normal colon crypt cells: a possible stem cell marker of human colon epithelium. Dig Dis Sci 48:1523–1529

    Article  PubMed  CAS  Google Scholar 

  64. Nusse R, Fuerer C, Ching W, Harnish K, Logan C, Zeng A, Ten Berge D, Kalani Y (2008) Wnt signaling and stem cell control. Cold Spring Harb Symp Quant Biol 73:59–66

    Article  PubMed  CAS  Google Scholar 

  65. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106–110

    Article  PubMed  CAS  Google Scholar 

  66. Okabe M, Sawamoto K, Imai T, Sakakibara S, Yoshikawa S, Okano H (1997) Intrinsic and extrinsic determinants regulating cell fate decision in developing nervous system. Dev Neurosci 19:9–16

    Article  PubMed  CAS  Google Scholar 

  67. Oliveira LR, de Castilho Fernandes A, Ribeiro-Silva A (2011) Chapter 1: Stem cells and cancer stem cells. In: Cancer stem cells – the cutting edge. InTech, Rijeka/Croatia

    Chapter  Google Scholar 

  68. Olsen CL, Hsu PP, Glienke J, Rubanyi GM, Brooks AR (2004) Hedgehog interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors. BMC Cancer 4:43

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  69. Papailiou J, Bramis KJ, Gazouli M, Theodoropoulos G (2011) Stem cells in colon cancer. A new era in cancer theory begins. Int J Colorectal Dis 26:1–11

    Article  PubMed  Google Scholar 

  70. Ponti D, Zaffaroni N, Capelli C, Daidone MG (2006) Breast cancer stem cells: an overview. Eur J Cancer 42(9):1219–1224

    Article  PubMed  CAS  Google Scholar 

  71. Potten CS, Kovacs L, Hamilton E (1974) Continuous labelling studies on mouse skin and intestine. Cell Tissue Kinet 7:271–283

    PubMed  CAS  Google Scholar 

  72. Potten CS (1977) Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature 269:518–521

    Article  PubMed  CAS  Google Scholar 

  73. Potten CS, Loeffler M (1990) Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 110:1001–1020

    PubMed  CAS  Google Scholar 

  74. Potten CS, Kellett M, Roberts SA, Rew DA, Wilson GD (1992) Measurement of in vivo proliferation in human colorectal mucosa using bromodeoxyuridine. Gut 33:71–78

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  75. Potten CS, Kellett M, Rew DA, Roberts SA (1992) Proliferation in human gastrointestinal epithelium using bromodeoxyuridine in vivo: data for different sites, proximity to a tumour, and polyposis coli. Gut 33:524–529

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  76. Potten CS, Owen G, Booth D (2002) Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci 115:2381–2388

    PubMed  CAS  Google Scholar 

  77. Potten CS, Booth C, Tudor GL, Booth D, Brady G, Hurley P, Ashton G, Clarke R, Sakakibara S, Okano H (2003) Identification of a putative intestinal stem cell and early lineage marker; musashi-1. Differentiation 71:28–41

    Article  PubMed  CAS  Google Scholar 

  78. Potten CS, Gandara R, Mahida YR, Loeffler M, Wright NA (2009) The stem cells of small intestinal crypts: where are they? Cell Prolif 42:731–750

    Article  PubMed  CAS  Google Scholar 

  79. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer and cancer stem cells. Nature 1;414(6859):105–111

    Google Scholar 

  80. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111–115

    Article  PubMed  CAS  Google Scholar 

  81. Ricci-Vitiani L, Fabrizi E, Palio E, De Maria R (2009) Colon cancer stem cells. J Mol Med (Berl) 87:1097–1104

    Article  Google Scholar 

  82. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459:262–265

    Article  PubMed  CAS  Google Scholar 

  83. Shay J, Wright W (2010) Telomeres and telomerase in normal and cancer stem cells. FEBS Lett 584(17):3819–3825

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  84. Shipitsin M, Polyak K (2008) The cancer stem cell hypothesis: in search of definitions, markers, and relevance. Lab Invest 88:459–463

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  85. Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, St Clair R, Baljevic M, White I, Jin DK, Chadburn A, Murphy AJ, Valenzuela DM, Gale NW, Thurston G, Yancopoulos GD, D’Angelica M, Kemeny N, Lyden D, Rafii S (2008) CD133 expression is not restricted to stem cells, and both CD133_ and CD133-metastatic colon cancer cells initiate tumors. J Clin Invest 118:2111–2120

    PubMed Central  PubMed  CAS  Google Scholar 

  86. Sikandar SS, Pate KT, Anderson S, Dizon D, Edwards RA, Waterman ML, Lipkin SM (2010) NOTCH signaling is required for formation and self-renewal of tumorinitiating cells and for repression of secretory cell differentiation in colon cancer. Cancer Res 70(4):1469–1478

    Article  PubMed  CAS  Google Scholar 

  87. Simons BD, Clevers H (2011) Stem cell self-renewal in intestinal crypt. Exp Cell Res 317:2719–2724

    Article  PubMed  CAS  Google Scholar 

  88. Takahashi H, Ishii H, Nishida N, Takemasa I, Mizushima T, Ikeda M, Yokobori T, Mimori K, Yamamoto H, Sekimoto M, Doki Y, Mori M (2011) Significance of Lgr5(+ve) cancer stem cells in the colon and rectum. Ann Surg Oncol 18(4):1166–1174

    Article  PubMed  Google Scholar 

  89. Takahashi-Yanaga F, Kahn M (2011) Targeting Wnt signaling: can we safely eradicate cancer stem cells? Clin Cancer Res 16(12):3153–3162

    Article  Google Scholar 

  90. Taylor RW, Barron MJ, Borthwick GM, Gospel A, Chinnery PF, Samuels DC, Taylor GA, Plusa SM, Needham SJ, Greaves LC, Kirkwood TB, Turnbull DM (2003) Mitochondrial DNA mutations in human colonic crypt stem cells. J Clin Invest 112:1351–1360

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  91. Tian H, Biehs B, Warming S, Leong KG, Rangell L, Klein OD, De Sauvage FJ (2011) A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478:255–259

    Article  PubMed  CAS  Google Scholar 

  92. Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP, Stassi G (2007) Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1(4):389–402

    Article  PubMed  CAS  Google Scholar 

  93. Todaro M, Francipane MG, Medema JP, Stassi G (2010) Colon cancer stem cells: promise of targeted therapy. Gastroenterology 138:2151–2162

    Article  PubMed  CAS  Google Scholar 

  94. Turashvili G, Bouchal J, Burkadze G, Kolar Z (2006) Wnt signaling pathway in mammary gland development and carcinogenesis. Pathobiology 73:213–223

    Article  PubMed  CAS  Google Scholar 

  95. van Es JH, Clevers H (2005) Notch and Wnt inhibitors as potential new drugs for intestinal neoplastic disease. Trends Mol Med 11:496–502

    Article  PubMed  CAS  Google Scholar 

  96. van der Flier LG, van Gijn ME, Hatzis P, Kujala P, Haegebarth A, Stange DE, Begthel H, van den Born M, Guryev V, Oving I, van Es JH, Barker N, Peters PJ, van de Wetering M, Clevers H (2009) Transcription factor achaete scute-like 2 controls intestinal stem cell fate. Cell 136:903–912

    Article  PubMed  CAS  Google Scholar 

  97. Vermeulen L, Todaro M, de Sousa MF, Sprick MR, Kemper K, Perez Alea M, Richel DJ, Stassi G, Medema JP (2008) Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci U S A 105(36):13427–13432

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  98. Vermeulen L, De Sousa EMF, van der Heijden M, Cameron K, de Jong JH, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, Sprick MR, Kemper K, Richel DJ, Stassi G, Medema JP (2010) Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol 12(5):468–476

    Article  PubMed  CAS  Google Scholar 

  99. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532

    Article  PubMed  CAS  Google Scholar 

  100. Vries RG, Huch M, Clevers H (2010) Stem cells and cancer of the stomach and intestine. Mol Oncol 4:373–384

    Article  PubMed  Google Scholar 

  101. Wang JC, Dick JE (2005) Cancer stem cells: lessons from leukemia. Trends Cell Biol 15(9):494–501

    Article  PubMed  CAS  Google Scholar 

  102. Wang JY, Wu CH, Lu CY, Hsieh J, Wu DC, Huang SY, Lin SR (2006) Molecular detection of circulating tumor cells in the peripheral blood of patients with colorectal cancer using RT-PCR: significance of the prediction of postoperative metastasis. World J Surg 30(6):1007–1013

    Article  PubMed  Google Scholar 

  103. Wicha MS, Liu S, Dontu G (2006) Cancer stem cells: an old idea-a paradigm shift. Cancer Res 66:1883–1890

    Article  PubMed  CAS  Google Scholar 

  104. Willis ND, Przyborski SA, Hutchison CJ et al (2008) Colonic and colorectal cancer stem cells: progress in the search for putative biomarkers. J Anat 213:59–65

    Article  PubMed Central  PubMed  Google Scholar 

  105. Zhu L, Gibso P, Currl DS, Tong Y, Richardson RJ, Bayazitov IT, Poppleton H, Zakharenko S, Ellison DW, Gilbertson RJ (2009) Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 457(7229):603–607

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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Correspondence to Esther Uña Cidón .

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© 2014 Springer Science+Business Media Dordrecht

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Cidón, E.U., Hickish, T. (2014). Stem Cells in Colon Cancer. In: Grande, E., Antón Aparicio, L. (eds) Stem Cells in Cancer: Should We Believe or Not?. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8754-3_6

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