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New Insights into the CD133 (Prominin-1) Expression in Mouse and Human Colon Cancer Cells

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Prominin-1 (CD133): New Insights on Stem & Cancer Stem Cell Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 777))

Abstract

Following its discovery as a cancer stem cell marker, CD133 has been widely studied for its role in colorectal tumorigenesis. Indeed, colon cancer remains one of the major causes of cancer-related disease and death worldwide, and there is a strong need for an improvement of current diagnostic, prognostic, and therapeutic strategies. Thus, efforts have been devoted to try to understand whether CD133 might play a role in human colorectal tumorigenesis and might contribute to a better management of colon cancer patients. This chapter reviews the current knowledge on CD133 expression in normal and cancer colon tissues, both in humans and mice, discussing apparently conflicting data reported in the two species. Moreover, a great attention is devoted to the available information regarding the functional role of CD133 in colon cancer cells. Finally, the proposed clinical applications of CD133, as a prognostic and/or predictive marker as well as a target for novel antineoplastic strategies in colorectal cancer, are discussed. Overall, the available data support a potential important role of CD133 as cancer stem cell marker in colon cancer cells and warrant future studies to verify its potential use in the routine clinical management of colon cancer patients.

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References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917

    Article  PubMed  CAS  Google Scholar 

  2. Center MM, Jemal A, Smith RA, Ward E (2009) Worldwide variations in colorectal cancer. CA Cancer J Clin 59:366–378

    Article  PubMed  Google Scholar 

  3. Meyerhardt JA, Mayer RJ (2005) Systemic therapy for colorectal cancer. N Engl J Med 352:476–487

    Article  PubMed  CAS  Google Scholar 

  4. Omura K (2008) Advances in chemotherapy against advanced or metastatic colorectal cancer. Digestion 77(Suppl 1):13–22

    Article  PubMed  CAS  Google Scholar 

  5. O’Connell MJ (2004) Current status of adjuvant therapy for colorectal cancer. Oncology (Williston Park) 18:751–755

    Google Scholar 

  6. Porter EM, Bevins CL, Ghosh D, Ganz T (2002) The multifaceted Paneth cell. Cell Mol Life Sci 59:156–170

    Article  PubMed  CAS  Google Scholar 

  7. Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434:843–850

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A et al (2002) The β-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111:241–250

    Article  PubMed  Google Scholar 

  10. Van der Flier LG, Sabates-Bellver J, Oving I, Haegebarth A, De Palo M, Anti M, Van Gijn ME, Suijkerbuijk S, Van de Wetering M, Marra G, Clevers H (2007) The intestinal Wnt/TCF signature. Gastroenterology 132:628–632

    Article  PubMed  Google Scholar 

  11. Fearon ER, Vogelstein B (1990) A genetic model for colorectal cancer tumorigenesis. Cell 61:759–767

    Article  PubMed  CAS  Google Scholar 

  12. Pinto D, Gregorieff A, Begthel H, Clevers H (2003) Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev 17:1709–1713

    Article  PubMed  CAS  Google Scholar 

  13. Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H (1997) Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC−/− colon carcinoma. Science 275:1784–1787

    Article  PubMed  CAS  Google Scholar 

  14. Haramis AP, Begthel H, van den Born M, van Es J, Jonkheer S, Offerhaus GJ, Clevers H (2004) De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 303:1684–1686

    Article  PubMed  CAS  Google Scholar 

  15. Boman BM, Walters R, Fields JZ, Kovatich AJ, Zhang T, Isenberg GA, Goldstein SD, Palazzo JP (2004) Colonic crypt changes during adenoma development in familial adenomatous polyposis: immunohistochemical evidence for expansion of the crypt base cell population. Am J Pathol 165:1489–1498

    Article  PubMed  Google Scholar 

  16. Dexter DL, Spremulli EN, Fligiel Z, Barbosa JA, Vogel R, VanVoorhees A, Calabresi P (1981) Heterogeneity of cancer cells from a single human colon carcinoma. Am J Med 71:949–956

    Article  PubMed  CAS  Google Scholar 

  17. 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 USA 105:13427–13432

    Article  PubMed  CAS  Google Scholar 

  18. Ailles LE, Weissman IL (2007) Cancer stem cells in solid tumors. Curr Opin Biotechnol 18:460–466

    Article  PubMed  CAS  Google Scholar 

  19. Zhu L, Gibson P, Currle 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 457:603–607

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  21. 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 445:111–115

    Article  PubMed  CAS  Google Scholar 

  22. Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T et al (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  CAS  Google Scholar 

  23. 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  CAS  Google Scholar 

  24. 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 219:427–434

    Article  PubMed  CAS  Google Scholar 

  25. Kojima M, Ishii G, Atsumi N, Fujii S, Saito N, Ochiai A (2008) Immunohistochemical detection of CD133 expression in colorectal cancer: a clinicopathological study. Cancer Sci 99:1578–1583

    Article  PubMed  CAS  Google Scholar 

  26. Li CY, Li BX, Liang Y, Peng RQ, Ding Y, Xu DZ, Zhang X, Pan ZZ, Wan DS, Zeng YX, Zhu XF, Zhang XS (2009) Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB. J Transl Med 7:56

    Article  PubMed  CAS  Google Scholar 

  27. 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 104:10158–10163

    Article  PubMed  CAS  Google Scholar 

  28. Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90:5002–5012

    PubMed  CAS  Google Scholar 

  29. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967

    Article  PubMed  CAS  Google Scholar 

  30. Shaked Y, Ciarrocchi A, Franco M, Lee CR, Man S, Cheung AM, Hicklin DJ, Chaplin D, Foster FS, Benezra R, Kerbel RS (2006) Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors. Science 313:1785–1787

    Article  PubMed  CAS  Google Scholar 

  31. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401

    Article  PubMed  CAS  Google Scholar 

  32. Puglisi MA, Sgambato A, Saulnier N, Rafanelli F, Barba M, Boninsegna A, Piscaglia AC, Lauritano C, Novi ML, Barbaro F, Rinninella E, Campanale C, Giuliante F, Nuzzo G, Alfieri S, Doglietto GB, Cittadini A, Gasbarrini A (2009) Isolation and characterization of CD133+ cell population within human primary and metastatic colon cancer. Eur Rev Med Pharmacol Sci 13(Suppl 1):55–62

    PubMed  Google Scholar 

  33. LaBarge MA, Bissell MJ (2008) Is CD133 a marker of metastatic colon cancer stem cells? J Clin Invest 118:2021–2024

    PubMed  CAS  Google Scholar 

  34. Liao Y, Hu X, Huang X, He C (2010) Quantitative analyses of CD133 expression facilitate researches on tumor stem cells. Biol Pharm Bull 33:738–742

    Article  PubMed  CAS  Google Scholar 

  35. Chu P, Clanton DJ, Snipas TS, Lee J, Mitchell E, Nguyen ML, Hare E, Peach RJ (2009) Characterization of a subpopulation of colon cancer cells with stem cell-like properties. Int J Cancer 24:1312–1321

    Article  Google Scholar 

  36. 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. Annals Surg Oncol 15:2927–2933

    Article  Google Scholar 

  37. Jaksch M, Múnera J, Bajpai R, Terskikh A, Oshima RG (2008) Cell cycle-dependent variation of a CD133 epitope in human embryonic stem cell, colon cancer, and melanoma cell lines. Cancer Res 68:7882–7886

    Article  PubMed  CAS  Google Scholar 

  38. Chao C, Carmical JR, Ives KL, Wood TG, Aronson JF, Gomez GA, Djukom CD, Hellmich MR (2012) CD133+ colon cancer cells are more interactive with the tumor microenvironment than CD133– cells. Lab Invest 92:420–436

    Article  PubMed  CAS  Google Scholar 

  39. Yang Z, Wang Z, Fan Y, Zheng Q (2012) Expression of CD133 in SW620 colorectal cancer cells is modulated by the microenvironment. Oncol Lett 4:75–79

    PubMed  CAS  Google Scholar 

  40. Sgambato A, Puglisi MA, Errico F, Rafanelli F, Boninsegna A, Rettino A, Genovese G, Coco C, Gasbarrini A, Cittadini A (2010) Post-translational modulation of CD133 expression during sodium butyrate-induced differentiation of HT29 human colon cancer cells: implications for its detection. J Cell Physiol 224:234–241

    PubMed  CAS  Google Scholar 

  41. Feng HL, Liu YQ, Yang LJ, Bian XC, Yang ZL, Gu B, Zhang H, Wang CJ, Su XL, Zhao XM (2010) Expression of CD133 correlates with differentiation of human colon cancer cells. Cancer Biol Ther 9:216–223

    Article  PubMed  CAS  Google Scholar 

  42. Corbeil D, Röper 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 

  43. Florek M, Haase M, Marzesco AM, Freund D, Ehninger G, Huttner WB, Corbeil D (2005) Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer. Cell Tissue Res 319:15–26

    Article  PubMed  CAS  Google Scholar 

  44. 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 

  45. Yi JM, Tsai HC, Glöckner SC, Lin S, Ohm JE, Easwaran H et al (2008) Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumors. Cancer Res 68:8094–8103

    Article  PubMed  CAS  Google Scholar 

  46. Kemper K, Sprick MR, de Bree M, Scopelliti A, Vermeulen L, Hoek M, Zeilstra J, Pals ST, Mehmet H, Stassi G, Medema JP (2010) The AC133 epitope, but not the CD133 protein, is lost upon cancer stem cell differentiation. Cancer Res 70:719–729

    Article  PubMed  CAS  Google Scholar 

  47. Sgambato A, Errico F, Caredda E, Puglisi MA, Cittadini A (2011) Divergent expression of CD133 in different studies: the need for a consensus panel? Int J Cancer 128:2240–2250

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  49. Hase K, Shatney C, Johnson D, Trollope M, Vierra M (1993) Prognostic value of tumor “budding” in patients with colorectal cancer. Dis Colon Rectum 36:627–635

    Article  PubMed  CAS  Google Scholar 

  50. Hostettler I, Zlobec I, Terracciano L, Lugli A (2010) ABCG5-positivity in tumor buds is an indicator of poor prognosis in node-negative colorectal cancer patients. World J Gastroenterol 16:732–739

    Article  PubMed  Google Scholar 

  51. Ong CW, Kim LG, Kong HH, Low LY, Iacopetta B, Soong R, Salto-Tellez M (2010) CD133 expression predicts for non-response to chemotherapy in colorectal cancer. Mod Pathol 23:450–457

    Article  PubMed  CAS  Google Scholar 

  52. Reggiani Bonetti L, Migaldi M, Caredda E, Ponz de Leon M, Di Gregorio C, Barresi V, Scannone D, Danese S, Cittadini A and Sgambato A (2012) Increased expression of CD133 is a strong predictor of poor outcome in stage I colorectal cancer patients. Scand J Gastroenterol 47: 1211–1217

    Google Scholar 

  53. Xi HQ, Zhao P (2011) Clinicopathological significance and prognostic value of EphA3 and CD133 expression in colorectal carcinoma. J Clin Pathol 64:498–503

    Article  PubMed  Google Scholar 

  54. Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Kawamoto A, Yasuda H, Morimoto Y, Fujikawa H, Inoue Y, Miki C, Kusunoki M (2010) Immunohistochemical features of CD133 expression: association with resistance to chemoradiotherapy in rectal cancer. Oncol Rep 24:345–350

    Article  PubMed  CAS  Google Scholar 

  55. Jao SW, Chen SF, Lin YS, Chang YC, Lee TY, Wu CC, Jin JS, Nieh S (2012) Cytoplasmic CD133 Expression is a Reliable Prognostic Indicator of Tumor Regression After Neoadjuvant Concurrent Chemoradiotherapy in Patients with Rectal Cancer. Ann Surg Oncol. [Epub ahead of print]

    Google Scholar 

  56. Artells R, Moreno I, Díaz T, Martínez F, Gel B, Navarro A, Ibeas R, Moreno J, Monzó M (2010) Tumour CD133 mRNA expression and clinical outcome in surgically resected colorectal cancer patients. Eur J Cancer 46:642–649

    Article  PubMed  CAS  Google Scholar 

  57. Dallas NA, Xia L, Fan F, Gray MJ, Gaur P, van Buren G 2nd, Samuel S, Kim MP, Lim SJ, Ellis LM (2009) Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Res 69:1951–1957

    Google Scholar 

  58. Neuzil J, Stantic M, Zobalova R, Chladova J, Wang X, Prochazka L, Dong L, Andera L, Ralph SJ (2007) Tumour-initiating cells vs. cancer ‘stem’ cells and CD133: what’s in the name? Biochem Biophys Res Commun 355:855–859

    Article  PubMed  CAS  Google Scholar 

  59. Nakamura K, Iinuma H, Aoyagi Y, Shibuya H, Watanabe T (2010) Predictive value of cancer stem-like cells and cancer-associated genetic markers for peritoneal recurrence of colorectal cancer in patients after curative surgery. Oncology 78:309–315

    Article  PubMed  CAS  Google Scholar 

  60. Iinuma H, Watanabe T, Mimori K, Adachi M, Hayashi N, Tamura J, Matsuda K, Fukushima R, Okinaga K, Sasako M, Mori M (2011) Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with Dukes’ stage B and C colorectal cancer. J Clin Oncol 29:1547–1555

    Article  PubMed  Google Scholar 

  61. Choi D, Lee HW, Hur KY, Kim JJ, Park GS, Jang SH, Song YS, Jang KS, Paik SS (2009) Cancer stem cell markers CD133 and CD24 correlate with invasiveness and differentiation in colorectal adenocarcinoma. World J Gastroenterol 15:2258–2264

    Article  PubMed  CAS  Google Scholar 

  62. Lugli A, Iezzi G, Hostettler I, Muraro MG, Mele V, Tornillo L, Carafa V, Spagnoli G, Terracciano L, Zlobec I (2010) Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer 103:382–390

    Article  PubMed  CAS  Google Scholar 

  63. Hermansen S, Christensen K, Jensen S, Kristensen B (2011) Inconsistent immunohistochemical expression patterns of four different CD133 antibody clones in glioblastoma. J Histochem Cytochem 59:391–407

    Article  PubMed  CAS  Google Scholar 

  64. Mak AB, Blakely KM, Williams RA, Penttilä PA, Shukalyuk AI, Osman KT, Kasimer D, Ketela T, Moffat J (2011) CD133 N-glycosylation processing contributes to cell-surface recognition of the primitive cell marker AC133. J Biol Chem 286:41046–41056

    Article  PubMed  CAS  Google Scholar 

  65. Kemper K, Versloot M, Cameron K, Colak S, de Sousa E, Melo F, de Jong JH, Bleackley J, Vermeulen L, Versteeg R, Koster J, Medema JP (2012) Mutations in the Ras-Raf Axis underlie the prognostic value of CD133 in colorectal cancer. Clin Cancer Res 18:3132–3141

    Article  PubMed  CAS  Google Scholar 

  66. Tanaka T, Kohno H, Suzuki R, Yamada Y, Sugie S, Mori H (2003) A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Cancer Sci 94:965–973

    Article  PubMed  CAS  Google Scholar 

  67. Arena V, Caredda E, Cufino V, Stigliano E, Scaldaferri F, Gasbarrini A, Cittadini A, Sgambato A (2011) Differential CD133 expression pattern during mouse colon tumorigenesis. Anticancer Res 31:4273–4275

    PubMed  Google Scholar 

  68. Waldron NN, Kaufman DS, Oh S, Inde Z, Hexum MK, Ohlfest JR, Vallera DA (2011) Targeting tumor-initiating cancer cells with dCD133KDEL shows impressive tumor reductions in a xenotransplant model of human head and neck cancer. Mol Cancer Ther 10:1829–1838

    Article  PubMed  CAS  Google Scholar 

  69. Sun J, Zhang C, Liu G, Liu H, Zhou C, Lu Y, Zhou C, Yuan L, Li X (2012) A novel mouse CD133 binding-peptide screened by phage display inhibits cancer cell motility in vitro. Clin Exp Metastasis 29:185–196

    Article  PubMed  Google Scholar 

  70. Matsumoto K, Arao T, Tanaka K, Kaneda H, Kudo K, Fujita Y, Tamura D, Aomatsu K, Tamura T, Yamada Y, Saijo N, Nishio K (2009) mTOR signal and hypoxia-inducible factor-1 alpha regulate CD133 expression in cancer cells. Cancer Res 69:7160–7164

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy

    Alessandro Sgambato M.D., Ph.D., Maddalena Corbi, Maria Svelto, Emanuele Caredda & Achille Cittadini

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  1. Alessandro Sgambato M.D., Ph.D.
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  2. Maddalena Corbi
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  3. Maria Svelto
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  4. Emanuele Caredda
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Correspondence to Alessandro Sgambato M.D., Ph.D. .

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  1. , Biotechnological Centre (BIOTEC), Dresden University of Technology, Fetscherstr. 74, Dresden, 01307, Sachsen, Germany

    Denis Corbeil

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Sgambato, A., Corbi, M., Svelto, M., Caredda, E., Cittadini, A. (2013). New Insights into the CD133 (Prominin-1) Expression in Mouse and Human Colon Cancer Cells. In: Corbeil, D. (eds) Prominin-1 (CD133): New Insights on Stem & Cancer Stem Cell Biology. Advances in Experimental Medicine and Biology, vol 777. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5894-4_10

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