EPITHELIAL-MESENCHYMAL TRANSITION, TRANSDIFFERENTIATION, REPROGRAMMING AND METAPLASIA: MODERN VIEW ON THE PROBLEM

The article portrays modern views on the problems of formation of metaplasia, transdifferentiation and reprogramming of cells and epithelial-mesenchymal transition on the basis of analysis of literature and the results of our own observations. Transdifferentiation in this article is considered as a kind of metaplasia, which is characterized by an irreversible transition of already differentiated cells into another type, due to the loss of one phenotype and the production of another. Metaplasia, in its broad aspect means the transformation of one cellular or tissue phenotype into another and occurs both through the transformation of stem cells and direct conversion of already differentiated cells. In addition to this metaplasia can be considered as a potentially reversible change, in which differentiated cell types are replaced by other differentiated cell types, usually better adapted to the transformed environmental conditions. Epithelial-mesenchymal transition is the process of epithelial cells alteration of epithelial phenotype to mesenchymal phenotype occurring in embryonic development, healing of wounds as well as in the pathological processes, including tumor progression and fibrosis. Epithelial-mesenchymal transition, metaplasia, transdifferentiation and cell reprogramming are complex dynamic pathophysiological processes that depend on the interaction of coordinated molecular signaling pathways. They play a key role during embryonic development, allowing cells to migrate to create the necessary tissues and organ development. This explains of the postnatal tissue changes that occur during wound healing and fibrosis, their involvement in the invasion and progression of tumors. Understanding the molecular mechanisms involved in the epithelial-mesenchymal transition, transdifferentiation, metaplasia and reprogramming can open up new perspectives in the study of carcinogenesis, the creation of effective targeted drugs that act purposefully on a particular signaling pathway or receptor. The features of metaplasia, transdifferentiation, epithelial-mesenchymal transition and cellular reprogramming considered in this article allow us to present only the general outlines of events that arise during intercellular interactions through the activation of various molecular genetic pathways. The annual discovery of new factors involved in intercellular interactions pose important tasks for researchers, which can be solved only with close international co-operation of the scientific community.

metaplasia, transdifferentiation, reprogramming, epithelial-mesenchymal transition

1. Аруин Л.И. О морфогенезе кишечной метаплазии слизистой оболочки желудка / Под ред. акад. АМН СССР В.Х. Василенко и проф. А.С. Логинова // Актуальные вопросы гасторэнтерологии: Сб. тр. - М., 1972. - С. 103-108.

2. Zeisberg M., Eric G.N. Biomarkers for epithelial-mesenchymal transitions. J. Clin. Invest. 2009; 119(6): 429-1437.

3. Thiery J.P., Sleeman J.P. Complex networks orchestrate epithelial-mesenchymal transitions. Nat. Rev. Mol. Cell Biol. 2006; 7(2): 131-142.

4. Hay E.D. An overview of epithelio-mesenchymal transformation. Acta Anat. 1995; 154: 8-20.

5. Пасечник Д.Г. Роль эпителиально-мезенхимального перехода в генезе хронической болезни почек и почечно-клеточного рака (проблемы и перспективы). Науковий вісник міжнародного гуманітарного університету. 2014; 6: 30-33.

6. Kalluri R., Robert A. Weinberg. The basics of epithelial-mesenchymal transition. J. Clin. Invest. 2009; 119(6): 1420-1428.

7. Cowin P., Rowlands T.M., Hatsell S.J. Cadherins and catenins in breast cancer. Curr Opin Cell Biol. 2005; 17(5): 499-508.

8. Bukholm I.K., Nesland J.M., Borresen-Dale A.L. Re-expression of E-cadherin, alpha-catenin and beta-catenin, but not of gamma-catenin, in metastatic tissue from breast cancer patients. J Pathol. 2000; 190(1): 15-19.

9. Zhang X.H., Liang X., Liang X.H. The Mesenchymal-Epithelial Transition During In Vitro Decidualization. Reprod. Sci. 2013; 20(4): 354.-360.

10. Cano A., Perez-Moreno M.A., Rodrigo I. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000; 2(2): 76-83.

11. Hajra K.M., Chen D.Y., Fearon E.R. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res. 2002; 62(6): 1613-1618.

12. Nieto M.A. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol.2002; 3(3): 155-166.

13. Pedersen K.B., Nesland J.M., Fodstad O., Maelandsmo G.M. Expression of S100A4, E-cadherin, alpha- and beta-catenin in breast cancer biopsies. Br J Cancer. 2002; 87(11): 1281-1286.

14. Yang M.H., Wu K.J. TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development. Cell Cycle. 2008; 7(14): 2090-2096.

15. Herreros A.G., Peiro S., Nassour M., Savagner P. Snail family regulation and epithelial mesenchymal transitions in breast cancer progression. J Mammary Gland Biol Neoplasia. 2010; 15(2): 135-147.

16. Jiang Y.G., Luo Y., He D.L. Role of Wnt/beta-catenin signaling pathway in epithelial-mesenchymal transition of human prostate cancer induced by hypoxia-inducible factor-1alpha. Int J Urol. 2007; 14(11): 1034-1039.

17. Batlle E., Sancho E., Franci C. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000; 2(2): 84-89.

18. Kurrey N.K., Bapat S.A. Snail and Slug are major determinants of ovarian cancer invasiveness at the transcription level. Gynecol Oncol. 2005; 97(1): 155-165.

19. Scherbakov A.M., Andreeva O.E., Shatskaya V.A., Krasil'nikov M.A. The relationships between snail and estrogen receptor signaling in breast cancer cells. Journal of cellular biochemistry.2012; 113(6): 2147-2155.

20. Vega S., Morales A.V., Ocana O.H. Snail blocks the cell cycle and confers resistance to cell death. Genes Dev. 2004; 18(10): 1131-1143.

21. Lamouille S., Jian Xu., Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nature Reviews Molecular Cell Biology. 2014; 15(): 178-196.

22. Российский онкологический портал профессионального общества [Электронный ресурс] Новости онкологии 06.03.2014/URL: http//www.rosoncoweb.ru/news/oncology/2014/03/06/ (Дата обращения: 06.03.2014)

23. Hood J.D., Cheresh D.A. Role of integrins in cell invasion and migration. Nat Rev Cancer. 2002; 2(2): 91-100.

24. Лазаревич Н.Л., Флейшман Д.И. Тканеспецифические транскрипционные факторы в прогрессии эпителиальных опухолей. Биохимия. 2008; 73(5): 735-750.

25. Eberhard D. Tosh D. Transdifferentiation and metaplasia as a paradigm for understanding development and disease. Cellular and molecular life sciences CMLS. 2008; 65(1): 33-40.

26. Kupffer C. Epithel und Drüsen des menschlichen Magens. Festschr. Arztl. Ver., München, 1883: 22.

27. Virchow. Uber Metaplasie. Virch. Arch. 1884: 97.

28. Beresford W.A. Direct transdifferentiation: Can cells change their phenotype without dividing? Cell Differ. Dev. 1990; 29: 81-93.

29. Chia-Ning Shen. Zoë D. Burke, David Tosh. Transdifferentiation, Metaplasia and Tissue Regeneration. Review. Organogenesis. 2004; 1(2): 36-44.

30. Eguchi G. Introduction: Transdifferentiation. Semin. Cell Biol. 1995; 6: 105-108.

31. Tosh D. Slack JMW How cells change their phenotype. Nat. Rev. Mol. Cell Biol. 2002; 3: 187-94.

32. Stemmermann G.N. Intestinal metaplasia of the stomach. A status report. Cancer. 1994; 74: 556-564.

33. Chan C.W.M., Newton W.A., Yinget L. Gastrointestinal differentiation marker Cytokeratin 20 is regulated by homeobox gene CDX1. PNAS. 2009; 106(6): 1936-1941.

34. Fukamachi H. Runx3 controls growth and differentiation of gastric epithelial cells in mammals. Dev. Growth and Differ. 2006; 48(1)1-13.

35. Mutoh Hiroyuki, Sakurai Shinji, Satoh Kiichi. Development of Gastric Carcinoma from Intestinal Metaplasia in Cdx2-transgenic Mice. Cancer Research. 2004; 64: 7740-7747.

36. Eda A., Osawa H., Yanaka I. Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia. J. Gastroenterol. 2002; 37(2): 94-100.

37. Samuel K., Kent M. Chu, John Moon Ching Luk. Expression of CDX2 and Li-cadherin in intestinal metaplasia and adenocarcinoma of the stomach. Proc. Amer. Assoc. Cancer Res. 2004; 45: 4242.

38. Gehring W.J., Affolter M., Bürglin T. "Homeodomain proteins". Annual review of biochemistry. 1994; 63: 487-526.

39. Babu М.М., Luscombe N.M., Aravind L., Gerstein M., Teichmann S.A. Structure and evolution of transcriptional regulatory networks. Curr. Opin. Struct. Biol. 2004; 14(3): 283-291.

40. Mutoh H., Sakurai S., Satoh K. Cdx1 induced intestinal metaplasia in the transgenic mouse stomach: comparative study with Cdx2 transgenic mice. Gut. 2004; 53: 1416-1423.

41. Patri'cia Mesquita, Almeida Raquel, Nuno Lunet. Metaplasia - A Transdifferentiation Process that Facilitates Cancer Development: The Model of Gastric Intestinal Metaplasia. Critical Reviews TM in Oncogenesis. 2006; 12(1-2): 3-26.

42. Dimmler A., Brabletz T. Transcription of Sonic Hedgehog, a Potential Factor for Gastric Morphogenesis and Gastric Mucosa Maintenance, Is Up-regulated in Acidic Conditions. Laboratory investigation. 2003; 83(12): 1829-1837.

43. Трумэн Д. Биохимия клеточной дифференцировки. М.: Мир, 1976. - 188 с.

44. Gutierrez-Gonzalez L., Wright N.A. Biology of intestinal metaplasia in 2008: More than a simple phenotypic alteration. Dig. Liver Dis. 2008; 40: 510-522.

45. Kirchner T., Müller S., Hattori T., Mukaisyo K., Papadopoulos T., Brabletz T., Jung A. Metaplasia, intraepithelial neoplasia and early cancer of the stomach are related to dedifferentiated epithelial cells defined by cytokeratin-7 expression in gastritis / A. Jung // Virchows Arch. 2001; 439(4): 512-522.

46. Houghton J., Stoicov С., Nomura S. Gastric cancer originating from bone marrow-derived cells. Science. 2004; 306: 1568-1571.

47. Wilmut I., Schnieke A.E., McWhir J. Viable offspring derived from fetal and adult mammalian cells. Nature. 1997; 385(6619): 810-813.

48. Cowan C.A., Atienza J., Melton D.A. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science. 2005; 309: 1369-1373.

49. Tada M., Takahama Y., Abe K. Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr. Biol. 2001; 11: 1553.

50. Gretchen V. Breakthrough of the year: Reprogramming cells. Science. 2008; 322: 1766-1767.

51. Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4): 663-676.

52. Shinya Y. Induced Pluripotent Stem Cells: Past, Present, and Future. Cell Stem Cell. 2012; 10(6): 678-684

53. Wong A.P., Rossant J. Generation of Lung Epithelium from Pluripotent Stem Cells. Current pathobiology reports. 2013; 1(2): 137-145.

54. Tilanthi M.J. MicroRNA-mediated in vitro and in vivo Direct Reprogramming of Cardiac Fibroblasts to Cardiomyocytes. Circ Res. 2012; 110(11): 1465-1473.

55. Ankur S., Shalu S. Adhesion strength-based, label-free isolation of human pluripotent stem cells. Nature Methods. 2013; 10: 438-444.

56. Mou H., Zhao R., Sherwood R., Ahfeldt T., Rajagopal J. Generation of multipotent lung and airway progenitors from mouse ESCs and patient-specific cystic fibrosis iPSCs. Cell stem cell. 2012; 10(4): 385-397.

57. Sheng C., Zheng Q., Wu J. Generation of dopaminergic neurons directly from mouse fibroblasts and fibroblast-derived neural progenitors. Cell Res; 2012; 22: 769-772.

58. Lin Cheng. Generation of neural progenitor cells by chemical cocktails and hypoxia. Cell Research. 2014; 24: 665-679.

59. Richard P., Halley-Stott, Vincent Pasque, Gurdon J.B. Nuclear reprogramming. Development. 2013; 140: 2468-2471.