Demystifying the Differences Between Tumor-Initiating Cells and Cancer Stem Cells in Colon Cancer

Abstract

Purpose of Review

Tumor-initiating cells and cancer stem cells refer to a subpopulation of self-renewing cells involved in tumor initiation and tumor maintenance, respectively. With this review, we aimed to define the functional and molecular differences between both cell types in the context of colon cancer.

Recent Findings

Recent evidence suggests that the two major stem cell populations in the normal intestinal crypt have tumor-initiating capacity and could be the cell-of-origin in colon cancer. Activation of the Wnt/β-catenin pathway (an early event in mouse intestinal carcinogenesis) in the crypt base columnar stem cells and reserve stem cells leads to adenoma formation, supporting a role in tumor initiation. On the other hand, colon cancer stem cells express several membrane markers facilitating their isolation by FACS and are associated with treatment resistance and higher metastatic potential.

Summary

Tumor-initiating cells and cancer stem cells express distinct markers, display discrete biological functions, and can be studied using different molecular and cellular approaches. While cancer stem cells may be derived from tumor-initiating cells, these terms are not necessarily interchangeable and more likely reflect a specific cell state.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683–91.

    Article  PubMed  Google Scholar 

  2. 2.

    Marley AR, Nan H. Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet. 2016;7(3):105–14.

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Johnson CM, Wei C, Ensor JE, Smolenski DJ, Amos CI, Levin B, et al. Meta-analyses of colorectal cancer risk factors. Cancer Causes Control CCC. 2013;24(6):1207–22.

    PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Dulai PS, Sandborn WJ, Gupta S. Colorectal cancer and dysplasia in inflammatory bowel disease: a review of disease epidemiology, pathophysiology, and management. Cancer Prev Res (Phila). 2016;9(12):887–94.

    Article  Google Scholar 

  5. 5.

    Long AG, Lundsmith ET, Hamilton KE. Inflammation and colorectal cancer. Curr Colorectal Cancer Rep. 2017;13(4):341–51.

    PubMed  PubMed Central  Article  Google Scholar 

  6. 6.

    Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61(5):759–67.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    Fodde R. The APC gene in colorectal cancer. Eur J Cancer Oxf Engl 1990. 2002;38(7):867–71.

    CAS  Google Scholar 

  8. 8.

    Carethers JM, Jung BH. Genetics and genetic biomarkers in sporadic colorectal cancer. Gastroenterology. 2015;149(5):1177–1190.e3.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138(6):2073–2087.e3.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    Sherwood L. Fundamentals of human physiology. 4th ed. Belmont: Brooks/Cole Cengage Learning; 2012.

    Google Scholar 

  11. 11.

    Marshman E, Booth C, Potten CS. The intestinal epithelial stem cell. BioEssays. 2002;24(1):91–8.

    PubMed  Article  Google Scholar 

  12. 12.

    Barker N, van Oudenaarden A, Clevers H. Identifying the stem cell of the intestinal crypt: strategies and pitfalls. Cell Stem Cell. 2012;11(4):452–60.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Valenta T, Degirmenci B, Moor AE, Herr P, Zimmerli D, Moor MB, et al. Wnt ligands secreted by subepithelial mesenchymal cells are essential for the survival of intestinal stem cells and gut homeostasis. Cell Rep. 2016;15(5):911–8.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature. 2011;469(7330):415–8.

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Durand A, Donahue B, Peignon G, Letourneur F, Cagnard N, Slomianny C, et al. Functional intestinal stem cells after Paneth cell ablation induced by the loss of transcription factor Math1 (Atoh1). Proc Natl Acad Sci U S A. 2012;109(23):8965–70.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A, et al. The β-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002;111(2):241–50.

    PubMed  Article  Google Scholar 

  17. 17.

    • Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449(7165):1003–7 Identification of Lgr5+ CBCs in the intestine.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    Tian H, Biehs B, Warming S, Leong KG, Rangell L, Klein OD, et al. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature. 2011;478(7368):255–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    • Takeda N, Jain R, LeBoeuf MR, Wang Q, Lu MM, Epstein JA. Interconversion between intestinal stem cell populations in distinct niches. Science. 2011;334(6061):1420–4 Identification of Hopx+ reserve ISCs in the intestine.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Yan KS, Chia LA, Li X, Ootani A, Su J, Lee JY, et al. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc Natl Acad Sci U S A. 2012;109(2):466–71.

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Hua G, Thin TH, Feldman R, Haimovitz-Friedman A, Clevers H, Fuks Z, et al. Crypt base columnar stem cells in small intestines of mice are radioresistant. Gastroenterology. 2012;143(5):1266–76.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Metcalfe C, Kljavin NM, Ybarra R, de Sauvage FJ. Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration. Cell Stem Cell. 2014;14(2):149–59.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Tao S, Tang D, Morita Y, Sperka T, Omrani O, Lechel A, et al. Wnt activity and basal niche position sensitize intestinal stem and progenitor cells to DNA damage. EMBO J. 2015;34(5):624–40.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    •• Sangiorgi E, Capecchi MR. Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet. 2008;40(7):915–20 Identification of Bmi1+ reserve ISCs in the intestine and demonstration that Bmi1+ cells can act as TICs.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    • Montgomery RK, Carlone DL, Richmond CA, Farilla L, Kranendonk ME, Henderson DE, et al. Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. Proc Natl Acad Sci U S A. 2011;108(1):179–84 Identification of Tert+ reserve ISCs in the intestine.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Potten CS, Hume WJ, Reid P, Cairns J. The segregation of DNA in epithelial stem cells. Cell. 1978;15(3):899–906.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Buczacki SJ, Zecchini HI, Nicholson AM, Russell R, Vermeulen L, Kemp R, et al. Intestinal label-retaining cells are secretory precursors expressing Lgr5. Nature. 2013;495(7439):65–9.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Li N, Nakauka-Ddamba A, Tobias J, Jensen ST, Lengner CJ. Mouse label-retaining cells are molecularly and functionally distinct from reserve intestinal stem cells. Gastroenterology. 2016;151(2):298–310

  29. 29.

    Yousefi M, Li N, Nakauka-Ddamba A, Wang S, Davidow K, Schoenberger J, et al. Msi RNA-binding proteins control reserve intestinal stem cell quiescence. J Cell Biol. 2016;215(3):401–13.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Powell AE, Wang Y, Li Y, Poulin EJ, Means AL, Washington MK, et al. The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell. 2012;149(1):146–58.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Yousefi M, Nakauka-Ddamba A, Berry CT, Li N, Schoenberger J, Simeonov KP, et al. Calorie restriction governs intestinal epithelial regeneration through cell-autonomous regulation of mTORC1 in reserve stem cells. Stem Cell Rep. 2018;10(3):703–11.

    CAS  Article  Google Scholar 

  32. 32.

    • Wong VW, Stange DE, Page ME, Buczacki S, Wabik A, Itami S, et al. Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nat Cell Biol. 2012;14(4):401–8 Identification of Lrig1+ ISCs in the intestine.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    • Poulin EJ, Powell AE, Wang Y, Li Y, Franklin JL, Coffey RJ. Using a new Lrig1 reporter mouse to assess differences between two Lrig1 antibodies in the intestine. Stem Cell Res. 2014;13(3 Pt A):422–30 Identification of Lrig1+ ISCs in the intestine.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Roche KC, Gracz AD, Liu XF, Newton V, Akiyama H, Magness ST. SOX9 maintains reserve stem cells and preserves radioresistance in mouse small intestine. Gastroenterology. 2015;149(6):1553–1563.e10.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Yousefi M, Li L, Lengner CJ. Hierarchy and plasticity in the intestinal stem cell compartment. Trends Cell Biol. 2017;27(10):753–64.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    •• Asfaha S, Hayakawa Y, Muley A, Stokes S, Graham TA, Ericksen RE, et al. Krt19(+)/Lgr5(−) cells are radioresistant cancer-initiating stem cells in the colon and intestine. Cell Stem Cell. 2015;16(6):627–38 Identification of Krt19+/Lgr5- ISCs in the intestine and demonstration that they can act as TICs.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. 37.

    •• Giroux V, Stephan J, Chatterji P, Rhoades B, Wileyto EP, Klein-Szanto AJ, et al. Mouse intestinal Krt15+ crypt cells are radio-resistant and tumor initiating. Stem Cell Rep. 2018;10(6):1947–58 Identification of Krt15+ ISCs in the intestine and demonstration that they can act as TICs.

    CAS  Article  Google Scholar 

  38. 38.

    van Es JH, Sato T, van de Wetering M, Lyubimova A, Nee AN, Gregorieff A, et al. Dll1+ secretory progenitor cells revert to stem cells upon crypt damage. Nat Cell Biol. 2012;14(10):1099–104.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  39. 39.

    Yan KS, Gevaert O, Zheng GXY, Anchang B, Probert CS, Larkin KA, et al. Intestinal enteroendocrine lineage cells possess homeostatic and injury-inducible stem cell activity. Cell Stem Cell. 2017;21(1):78–90.e6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    Tetteh PW, Basak O, Farin HF, Wiebrands K, Kretzschmar K, Begthel H, et al. Replacement of lost Lgr5-positive stem cells through plasticity of their enterocyte-lineage daughters. Cell Stem Cell. 2016;18(2):203–13.

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Yu S, Tong K, Zhao Y, Balasubramanian I, Yap GS, Ferraris RP, et al. Paneth cell multipotency induced by notch activation following injury. Cell Stem Cell. 2018;23(1):46–59.e5.

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Rycaj K, Tang DG. Cell-of-origin of cancer versus cancer stem cells: assays and interpretations. Cancer Res. 2015;75(19):4003–11.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Visvader JE, Lindeman GJ. Cancer stem cells: current status and evolving complexities. Cell Stem Cell. 2012;10(6):717–28.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Eun K, Ham SW, Kim H. Cancer stem cell heterogeneity: origin and new perspectives on CSC targeting. BMB Rep. 2017;50(3):117–25.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    Fonseca NA, Cruz AF, Moura V, Simões S, Moreira JN. The cancer stem cell phenotype as a determinant factor of the heterotypic nature of breast tumors. Crit Rev Oncol Hematol. 2017;113:111–21.

    PubMed  Article  Google Scholar 

  46. 46.

    Fearnhead NS, Britton MP, Bodmer WF. The ABC of APC. Hum Mol Genet. 2001;10(7):721–33.

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Walz S, Lorenzin F, Morton J, Wiese KE, von Eyss B, Herold S, et al. Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles. Nature. 2014;511(7510):483–7.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Jackstadt R, Sansom OJ. Mouse models of intestinal cancer. J Pathol. 2016;238(2):141–51.

    PubMed  Article  Google Scholar 

  49. 49.

    McCart AE, Vickaryous NK, Silver A. Apc mice: models, modifiers and mutants. Pathol Res Pract. 2008;204(7):479–90.

    PubMed  Article  Google Scholar 

  50. 50.

    Karim BO, Huso DL. Mouse models for colorectal cancer. Am J Cancer Res. 2013;3(3):240–50.

    PubMed  PubMed Central  Google Scholar 

  51. 51.

    Moser AR, Pitot HC, Dove WF. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science. 1990;247(4940):322–4.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Andreu P, Colnot S, Godard C, Gad S, Chafey P, Niwa-Kawakita M, et al. Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine. Development. 2005;132(6):1443–51.

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    •• Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009;457(7229):608–11 Demonstration that Lgr5+ cells can act as TICs in colon cancer.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    •• Powell AE, Vlacich G, Zhao ZY, McKinley ET, Washington MK, Manning HC, et al. Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in multiple distal colonic tumors with features of familial adenomatous polyposis. Am J Physiol Liver Physiol. 2014;307(1):G16–23 Demonstration that Lrig+ cells can act as TICs in colon cancer.

    CAS  Google Scholar 

  55. 55.

    •• O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445(7123):106–10 Demonstration that CD133 marks CSCs in colon cancer.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  56. 56.

    •• Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111–5 Demonstration that CD133 marks CSCs in colon cancer.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Ong CW, Kim LG, Kong HH, Low LY, Iacopetta B, Soong R, et al. CD133 expression predicts for non-response to chemotherapy in colorectal cancer. Mod Pathol. 2010;23(3):450–7.

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Du L, Wang H, He L, Zhang J, Ni B, Wang X, et al. CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res Off J Am Assoc Cancer Res. 2008;14(21):6751–60.

    CAS  Article  Google Scholar 

  59. 59.

    Dylla SJ, Beviglia L, Park I-K, Chartier C, Raval J, Ngan L, et al. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS ONE [Internet]. 2008;3(6) [cited 2018 Sep 28] Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2413402/.

  60. 60.

    •• Dalerba P, Dylla SJ, Park I-K, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A. 2007;104(24):10158–63 Demonstration that CD166 marks CSCs in colon cancer.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  61. 61.

    •• Haraguchi N, Ohkuma M, Sakashita H, Matsuzaki S, Tanaka F, Mimori K, et al. CD133+CD44+ population efficiently enriches colon cancer initiating cells. Ann Surg Oncol. 2008;15(10):2927–33 Demonstration that CD44 marks CSCs in colon cancer.

    PubMed  Article  Google Scholar 

  62. 62.

    LIU D, SUN J, ZHU J, ZHOU H, ZHANG X, ZHANG Y. Expression and clinical significance of colorectal cancer stem cell marker EpCAMhigh/CD44+ in colorectal cancer. Oncol Lett. 2014;7(5):1544–8.

    PubMed  PubMed Central  Article  Google Scholar 

  63. 63.

    Jing F, Kim HJ, Kim CH, Kim YJ, Lee JH, Kim HR. Colon cancer stem cell markers CD44 and CD133 in patients with colorectal cancer and synchronous hepatic metastases. Int J Oncol. 2015;46(4):1582–8.

    CAS  PubMed  Article  Google Scholar 

  64. 64.

    Levin TG, Powell AE, Davies PS, Silk AD, Dismuke AD, Anderson EC, et al. Characterization of the intestinal cancer stem cell marker CD166 in the human and mouse gastrointestinal tract. Gastroenterology. 2010;139(6):2072–2082.e5.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  65. 65.

    Ni C, Zhang Z, Zhu X, Liu Y, Qu D, Wu P, et al. Prognostic value of CD166 expression in cancers of the digestive system: a systematic review and meta-analysis. PLoS One. 2013;8(8):e70958.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. 66.

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. 67.

    Han S, Yang W, Zong S, Li H, Liu S, Li W, et al. Clinicopathological, prognostic and predictive value of CD166 expression in colorectal cancer: a meta-analysis. Oncotarget. 2017;8(38):64373–84.

    PubMed  PubMed Central  Google Scholar 

  68. 68.

    Tomita H, Tanaka K, Tanaka T, Hara A. Aldehyde dehydrogenase 1A1 in stem cells and cancer. Oncotarget. 2016;7(10):11018–32.

    PubMed  PubMed Central  Article  Google Scholar 

  69. 69.

    •• Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, et al. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res. 2009;69(8):3382–9 Demonstration that ALDH1 marks CSCs in colon cancer.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. 70.

    Deng S, Yang X, Lassus H, Liang S, Kaur S, Ye Q, et al. Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers. PLoS One. 2010;5(4):e10277.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  71. 71.

    de la Haba-Rodríguez J, Macho A, Calzado MA, Blázquez MV, Gómez MA, Muñoz EE, et al. Soluble dipeptidyl peptidase IV (CD-26) in serum of patients with colorectal carcinoma. Neoplasma. 2002;49(5):307–11.

    PubMed  PubMed Central  Google Scholar 

  72. 72.

    Lam CS-C, Cheung AH-K, Wong SK-M, Wan TM-H, Ng L, Chow AK-M, et al. Prognostic significance of CD26 in patients with colorectal cancer. PLoS One. 2014;9(5):e98582.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  73. 73.

    Lieto E, Galizia G, Orditura M, Romano C, Zamboli A, Castellano P, et al. CD26-positive/CD326-negative circulating cancer cells as prognostic markers for colorectal cancer recurrence. Oncol Lett. 2015;9(2):542–50.

    PubMed  Article  PubMed Central  Google Scholar 

  74. 74.

    •• Pang R, Law WL, Chu ACY, Poon JT, Lam CSC, Chow AKM, et al. A subpopulation of CD26+ cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell. 2010;6(6):603–15 Demonstration that CD26 marks CSCs in colon cancer with high metastatic capacities.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  75. 75.

    Kozovska Z, Gabrisova V, Kucerova L. Colon cancer: cancer stem cells markers, drug resistance and treatment. Biomed Pharmacother. 2014;68(8):911–6.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  76. 76.

    Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood. 1997;90(12):5013–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. 77.

    Wielenga VJ, Smits R, Korinek V, Smit L, Kielman M, Fodde R, et al. Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. Am J Pathol. 1999;154(2):515–23.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. 78.

    Yan Y, Zuo X, Wei D. Concise review: emerging role of CD44 in cancer stem cells: a promising biomarker and therapeutic target. Stem Cells Transl Med. 2015;4(9):1033–43.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  79. 79.

    •• Todaro M, Gaggianesi M, Catalano V, Benfante A, Iovino F, Biffoni M, et al. CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell. 2014;14(3):342–56 Demonstration that CD44v6+ cells are colon CSCs with high metastatic capacities.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  80. 80.

    Deng Y, Zhou J, Fang L, Cai Y, Ke J, Xie X, et al. ALDH1 is an independent prognostic factor for patients with stages II-III rectal cancer after receiving radiochemotherapy. Br J Cancer. 2014;110(2):430–4.

    CAS  PubMed  Article  Google Scholar 

  81. 81.

    Qureshi-Baig K, Ullmann P, Haan S, Letellier E. Tumor-initiating cells: a criTICal review of isolation approaches and new challenges in targeting strategies. Mol Cancer [Internet]. 2017;16 [cited 2018 Sep 28] Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314476/.

  82. 82.

    Visvader JE. Cells of origin in cancer. Nature. 2011;469(7330):314–22.

    CAS  PubMed  Article  Google Scholar 

  83. 83.

    Huels DJ, Sansom OJ. Stem vs non-stem cell origin of colorectal cancer. Br J Cancer. 2015;113(1):1–5.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  84. 84.

    Baccelli I, Trumpp A. The evolving concept of cancer and metastasis stem cells. J Cell Biol. 2012;198(3):281–93.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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Correspondence to Véronique Giroux.

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This article is part of the Topical Collection on Basic Science Foundations in Colorectal Cancer

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Chatterji, P., Douchin, J. & Giroux, V. Demystifying the Differences Between Tumor-Initiating Cells and Cancer Stem Cells in Colon Cancer. Curr Colorectal Cancer Rep 14, 242–250 (2018). https://doi.org/10.1007/s11888-018-0421-x

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Keywords

  • Colon cancer
  • Tumor-initiating cells
  • Cancer stem cells
  • Cancer relapse
  • Cell-of-origin
  • Drug resistance