Role of stem cells in large bowel carcinogenesis

Сancer stem cells (CSC) play a significant role in the development and progression of colorectal cancer. They are capable of self-senewal and multipotent differentiation. CSC can be formed from stem cells or mutant by dedifferentiation of crypt epithelial cells. Recently, much attention is paid to CSC in colon cancer, but very little has been published regarding their expression in colon polyps. In 2010 The World Health Organization attributed the so-called serrated lesions, including hyperplastic polyp, serrated sessile adenoma and traditional serrated adenoma to a group of precancerous lesions of the colon in addition to the classical tubular, villous and tubulo-villous adenomas. Despite the large number of publications devoted to the newly selected category, a full understanding of the processes involved in the formation of polyps and their progression into colon cancer, there is still no. Identification of CSC in colon polyps will assess their potential malignancy conduct adequate therapy, determine the amount of the operation and further treatment strategy. This in turn will contribute to the early detection and prevention of cancer. Identification of CSC, an assessment of their localization and distribution in tubular adenomas, serrated adenoma broad-based, traditional serrated adenoma and hyperplastic polyps allow to evaluate the potential of malignancy and prognosis for each of the polyps. In this regard, the definition of markers characteristic of colon CSC, is interesting not only from a scientific, but also from a practical point of view.

1. Fanali C., Lucchetti D., Farina M. et al. Cancer stem cells in colorectal cancer from pathogenesis to therapy: controversies and perspectives. World J Gastroenterol 2014;20(4):923–42.

2. Vogelstein B., Fearon E. R., Hamilton S. R. et al. Genetic alterations during olorectaltumor development. N Engl J Med 1988;319(9):525–32.

3. Wong N. A., Pignatelli M. Beta-catenin – a linchpin in colorectal carcinogenesis? Am J Pathol 2002;160(2):389–401.

4. Fang X., Yu W., Li L. et al. ChIP-seq and functional analysis of the SOX2 gene in colorectal cancers. OMICS 2010;14(4):369–84.

5. Arends M. J. Pathways of colorectal carcinogenesis. Appl Immunohistochem Mol Morphol 2013;21(2):97–102.

6. Snover D. C., Ahnen D. J., Burt R. W., Odze R. D. Serrated polyps of the colon and rectum and serrated polyposis. In book: WHO classification of tumours of the digestive system. Bosman F. T., Carneiro F., Hruban R. H. et al. (eds.). Lyon, France: IARC, 2010. Pp. 160–5.

7. Caruso M., Fung K. Y., Moore J. et al. Claudin-1 Expression Is Elevated in Colorectal Cancer Precursor Lesions Harboring the BRAF V600E Mutation. Transl Oncol 2014;7(4):456–63.

8. Jiao Y. F., Nakamura S., Sugai T. et al. Serrated adenoma of the colorectum undergoes a proliferation versus differentiation process: new conceptual interpretation of morphogenesis. Oncology 2008;74 (3–4):127–34.

9. Bettington M., Walker N., Clouston A. et al. The serrated pathway to colorectal arcinoma: current concepts and challenges. Histopathology 2013;62(3):367–86.

10. Харлова О. А., Данилова Н. В.,Мальков П. Г. и др. Зубчатые образования (serrated lesions) толстой кишки. Архив патологии 2015;1:60–8. [Kharlova O. A., Danilova N. V., Malkov P. G. et al. Serrated lesions of the colon. Arkhiv patologii = Pathology Archive 2015;1:60–8. (In Russ.)].

11. Bettington M. L., Walker N. I., Rosty C. et al. A clinicopathological and molecular analysis of 200 traditional serrated adenomas. Mod Pathol 2015;28(3):414–27.

12. Conesa-Zamora P., Garcia-Solano J., Garcia-Garcia F. et al. Expression profiling shows differential molecular pathways and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma. Int J Cancer 2013;132(2):297–307.

13. Safaee Ardekani G., Jafarnejad S. M., Tan L. et al. The prognostic value of BRAF mutation in colorectal cancer and melanoma: systematic review and meta-analysis. PLoS One 2012;7(10):e47054.

14. 13. Vermeulen L., Todaro M., de Sousa Mello F. et al. Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci USA 2008;105(36):13427–32.

15. Antoniou A., Hebrant A., Dom G. et al. Cancer stem cells, a fuzzy evolving concept: a cell population or a cell property? Cell Cycle 2013;12(24):3743–8.

16. Gangemi R., Paleari L., Orengo A. M. et al. Cancer stem cells: a new paradigm for nderstanding tumor growth and progression and drug resistance. Curr Med Chem 2009;16(14):1688–703.

17. Puglisi M. A., Tesori V., Lattanzi W. et al. Colon cancer stem cells: controversies and perspectives. World J Gastroenterol 2013;19(20):2997–3006.

18. Cicalese A., Bonizzi G., Pasi C. E. et al. The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell 2009;138(6):1083–95.

19. Botchkina G. Colon cancer stem cellsfrom basic to clinical application. Cancer Lett 2013;338(1):127–40.

20. Blanpain C., Horsley V., Fuchs E. Epithelial stem cells: turning over new leaves. Cell 2007;128(3):445–58.

21. Vries R. G., Huch M., Clevers H. Stem cells and cancer of the stomach and intestine. Mol Oncol 2010;4(5):373–84.

22. Dexter D. L., Spremulli E. N., Fligiel Z. et al. Heterogeneity of cancer cells from a single human colon carcinoma. Am J Med 1981;71(6):949–56.

23. Barker N., Ridgway R. A., van Es J. H. et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 2009;457(7229):608–11.

24. Shih I. M., Wang T. L., Traverso G. et al. Top-down morphogenesis of colorectal tumors. Proc Natl Acad Sci USA 2001;98(5):2640–5.

25. Mohammadi M., Bzorek M., Bonde J. H. et al. The stem cell marker CD133 is highly expressed in sessile serrated adenoma and its borderline variant compared with hyperplastic polyp. J Clin Pathol 2013;66(5):403–8.

26. Potten C. S., Booth C., Tudor G. L. et al. Identification of a putative intestinal stem cell and early lineage marker; musashi-1. Differentiation 2003;71(1):28–41.

27. Todaro M., Francipane M. G., Medema J. P., Stassi G. Colon cancer stem cells: promise of targeted therapy. Gastroenterology 2010;138(6):2151–62.

28. Nishimura S., Wakabayashi N., Toyoda K. et al. Expression of Musashi-1 in human normal colon crypt cells: a possible stem cell marker of human colon epithelium. Dig Dis Sci 2003;48(8):1523–9.

29. Femia A. P., Dolara P., Salvadori M. et al. Expression of LGR-5, MSI-1 and DCAMKL-1, putative stem cell markers, in the early phases of 1,2-dimethylhydrazineinduced rat colon carcinogenesis: correlation with nuclear beta-catenin. BMC Cancer 2013;13:48.

30. Femia A. P., Luceri C., Toti S. et al. Gene expression profile and genomic alterations in colonic tumours induced by 1,2-dimethylhydrazine (DMH) in rats. BMC Cancer 2010;10:194.

31. Murayama M., Okamoto R., Tsuchiya K. et al. Musashi-1 suppresses expression of Paneth cell-specific genes in human intestinal epithelial cells. J Gastroenterol 2009;44(3):173–82.

32. Weina K., Utikal J. SOX2 and cancer: current research and its implications in the clinic. Clin Transl Med 2014;3:19.

33. Sarkar A., Hochedlinger K. The SOX family of transcription factors: versatile regulators of stem and progenitor cell fate. Cell Stem Cell 2013;12(1):15–30.

34. Toschi L., Finocchiaro G., Nguyen T. T. et al. Increased SOX2 gene copy number is associated with FGFR1 and PIK3CA gene gain in non-small cell lung cancer and predicts improved survival in early stage disease. PLoS One 2014;9(4):e95303.

35. Neumann J., Bahr F., Horst D. et al. SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer. BMC Cancer 2011;11:518.

36. Park E. T., Gum J. R., Kakar S. et al. Aberrant expression of SOX2 upregulates MUC5AC gastric foveolar mucin in mucinous cancers of the colorectum and related lesions. Int J Cancer 2008;122(6):1253–60.

37. Saigusa S., Tanaka K., Toiyama Y. et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann Surg Oncol 2009;16(12):3488–98.

38. Han X., Fang X., Lou X. et al. Silencing SOX2 induced mesenchymal-epithelial transition and its expression predicts liver and lymph node metastasis of CRC patients. PLoSOne 2012;7(8):e41335.

39. Avilion A. A., Nicolis S. K., Pevny L. H. et al. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev 2003;17(1):126–40.

40. Liu H., Du L., Wen Z. et al. Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the mTOR signaling pathway. Int J Mol Med 2013;32(1):59–66.

41. Huang E. H., Hynes M. J., Zhang T. 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.

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

43. Kang E. J., Jung H., Woo O. H. et al. Association of aldehyde dehydrogenase 1 expression and biologically aggressive features in breast cancer. Neoplasma 2014; 61(3):352–62.

44. Goossens-Beumer I. J., Zeestraten E. C., Benard A. et al. Clinical prognostic value of combined analysis of Aldh1, Survivin, and EpCAM expression in colorectal cancer. Br J Cancer 2014;110(12):2935–44.

45. Fitzgerald T. L., Rangan S., Dobbs L. et al. The impact of Aldehyde dehydrogenase 1 expression on prognosis for metastatic colon cancer. J Surg Res 2014;192(1):82–9.

46. Nestl A., Von Stein O. D., Zatloukal K. et al. Gene expression patterns associated with the metastatic phenotype in rodent and human tumors. Cancer Res 2001;61(4):1569–77.

47. Lim S. C., Oh S. H. The role of CD24 in various human epithelial neoplasias. Pathol Res Pract 2005;201(7):479–86.

48. Weichert W., Denkert C., Burkhardt M. et al. Cytoplasmic CD24 expression in colorectal cancer independently correlates with shortened patient survival. Clin Cancer Res 2005;11(18):6574–81.

49. Sagiv E., Starr A., Rozovski U. et al. Targeting CD24 for treatment of colorectal and pancreatic cancer by monoclonal antibodies or small interfering RNA. Cancer Res 2008;68(8):2803–12.

50. Yeung T. M., Gandhi S. C., Wilding J. L. et al. Cancer stem cells from colorectal ancerderived cell lines. Proc Natl Acad Sci USA 2010;107(8):3722–7.

51. Sneath R. J., Mangham D. C. The normal structure and function of CD44 and its role in neoplasia. Mol Pathol 1998;51(4):191–200.

52. Du L., Wang H., He L. et al. CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res 2008;14(21):6751–60.

53. Zeilstra J., Joosten S. P., Dokter M. et al. Deletion of the WNT target and cancer stem cell marker CD44 in Apc (Min/+) mice attenuates intestinal tumorigenesis. Cancer Res 2008;68(10):3655–61.

54. Wang J. Y., Chang C. C., Chiang C. C. et al. Silibinin suppresses the maintenance of colorectal cancer stem-like cells by inhibiting PP2A/AKT/mTOR pathways. J Cell Biochem 2012;113(5):1733–43.

55. Baker A. M., Graham T. A., Elia G. et al. Characterization of LGR5 stem cells in colorectal adenomas and carcinomas. Sci Rep 2015;5:8654.

56. Nagano O., Saya H. Mechanism and biological significance of CD44 cleavage. Cancer Sci 2004;95(12):930–5.

57. Harada N., Mizoi T., Kinouchi M. et al. Introduction of antisense CD44S CDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastatic colon carcinoma cells. Int J Cancer 2001; 91(1):67–75.

58. Dallas M. R., Liu G., Chen W. C. et al. Divergent roles of CD44 and carcinoembryonic antigen in colon cancer metastasis. FASEB J 2012;26(6):2648–56.

59. Ropponen K. M., Eskelinen M. J., Lipponen P. K. et al. Expression of CD44 and variant proteins in human colorectal cancer and its relevance for prognosis. Scand J Gastroenterol 1998;33(3):301–9.

60. Huh J. W., Kim H. R., Kim Y. J. et al. Expression of standard CD44 in human colorectal carcinoma: association with prognosis. Pathol Int 2009;59(4):241–6.