Epithelial-mesenchymal transition as a fundamental underlying pathogenic process in COPD airways: Fibrosis, remodeling and cancer

Expert Review of Respiratory Medicine

Volumn 8, Issue 5, 2014, Pages 547-559

  Nowrin, Kaosia ^a,b   Sohal, Sukhwinder Singh ^a   Peterson, Gregory ^a,b   Patel, Rahul ^b   Walters, Eugene Haydn ^a  

^a UNIVERSITY OF TASMANIA   (Australia)

^b UNIVERSITY OF TASMANIA   (Australia)

Author keywords

COPD; epithelial mesenchymal transition; Smads; smoking; transcription factors; catenin

Indexed keywords

BETA CATENIN; INTEGRIN LINKED KINASE; SMAD PROTEIN; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA; UROKINASE; WNT PROTEIN;

AIRWAY OBSTRUCTION; AIRWAY REMODELING; CHRONIC OBSTRUCTIVE LUNG DISEASE; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; IN VITRO STUDY; LUNG CANCER; LUNG FIBROSIS; PATHOGENESIS; PREVALENCE; PROTEIN EXPRESSION; PROTEIN FAMILY; REVIEW; SIGNAL TRANSDUCTION; SMOKING; WNT SIGNALING PATHWAY; FIBROSIS; LUNG; PATHOLOGY; PATHOPHYSIOLOGY; RESPIRATORY SYSTEM; RESPIRATORY TRACT TUMOR;

EPITHELIAL-MESENCHYMAL TRANSITION; FIBROSIS; HUMANS; LUNG; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; RESPIRATORY SYSTEM; RESPIRATORY TRACT NEOPLASMS;

EID: 84907052579     PISSN: 17476348     EISSN: 17476356     Source Type: Journal    
DOI: 10.1586/17476348.2014.948853     Document Type: Review

References (95)

1. Lundback B, Lindberg A, Lindström M, et al. Not 15 but 50% of smokers. develop COPD?-Report from the Obstructive lung disease in Northern Sweden studies. Respir Med 2003;97(2):115-22
2. Laniado-Laborin R. Smoking and chronic obstructive pulmonary disease (COPD). parallel epidemics of the 21 century. Int J Environ Res Public Health 2009;6(1): 209-24
3. World Health Organization (WHO). Chronic obstructive pulmonary disease (COPD). 2013. Available from: www.who. int/respiratory/copd/en/[Last accessed 11 December 2013]
4. Petty DT. The History of COPD. Second Wind Newsletter. 2005. Available from: www.perf2ndwind.org/html/news/2005/April-May/Page2.html
5. Spriggs EA. Hutchinson J, the inventor of the spirometer-hisnorthcountrybackground, life in London, and scientific achievements. Med Hist 1977;21(4):357-64
6. Reid L. Pathology of chronic bronchitis. Proc R Soc Med 1956;49(10):771-3
7. Reid L. Measurement of the bronchial mucous gland layer: a diagnostic yardstick in chronic bronchitis. Thorax 1960;15: 132-41
8. OShaughnessy TC, Ansari TW, Barnes NC, Jeffery PK. Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1. Am J Respir Crit Care Med 1997;155(3):852-7
9. Saetta M, Di Stefano A, Maestrelli P, et al. Activated T-lymphocytes and macrophages in bronchial mucosa of subjects with chronic bronchitis. Am Rev Respir Dis 1993;147(2):301-6
10. Norrby K. Mast cells and angiogenesis. APMIS 2002;110(5):355-71
11. Soltani A, Ewe YP, Lim ZS, et al. Mast cells in COPD airways: relationship to bronchodilator responsiveness and angiogenesis. Eur Respir J 2012;39(6): 1361-7
12. Sohal SS, Reid D, Soltani A, et al. Changes in airway histone deacetylase2 in smokers and COPD with inhaled corticosteroids: a randomized controlled trial. PLoS One 2013;8(5):e64833
13. Sommerhoff CP, Nadel JA, Basbaum CB, Caughey GH. Neutrophil elastase and cathepsin G stimulate secretion from cultured bovine airway gland serous cells. J Clin Invest 1990;85(3):682-9
14. Sohal SS, Tan D, Muller HK, et al. Neutrophil numbers are decreased in bronchial biopsies from patients with COPD. Eur Respir J 2013;42(Suppl 57): 104s
15. Reid DW, Wen Y, Johns DP, et al. Bronchodilator reversibility, airway eosinophilia and anti-inflammatory effects of inhaled fluticasone in COPD are not related. Respirology (Carlton, Vic.) 2008; 13(6):799-809
16. McDonough JE, Yuan R, Suzuki M, et al. Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N Engl J Med 2011;365(17):1567-75
17. Sohal SS, Reid D, Soltani A, et al. Reticular basement membrane fragmentation and potential epithelial mesenchymal transition is exaggerated in the airways of smokers with chronic obstructive pulmonary disease. Respirology 2010;15(6):930-8
18. Chen D, Gassenmaier M, Maruschke M, et al. Expression and prognostic significance of a comprehensive epithelial-mesenchymal transition gene set in renal cell carcinoma. J Urol 2014;191(2):479-86
19. Ding W, You H, Dang H, et al. Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion. Hepatology 2010;52(3):945-53
20. Nakajima S, Doi R, Toyoda E, et al. N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma. Clin Cancer Res 2004;10(12 Pt 1):4125-33
21. Zeng Q, Li W, Lu D, et al. CD146, an epithelial-mesenchymal transition inducer, is associated with triple-negative breast cancer. Proc Natl Acad Sci USA 2012;109(4): 1127-32
22. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell 2009;139(5):871-90
23. De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 2013;13(2): 97-110
24. Nieto MA. Epithelial plasticity: a common theme in embryonic and cancer cells. Science 2013;342(6159):1234850
25. Young RP, Whittington CF, Hopkins RJ, et al. Chromosome 4q31 locus in COPD is also associated with lung cancer. Eur Respir J 2010;36(6):1375-82
26. Garcia Garcia Mdel C, et al. Cancer in chronic obstructive pulmonary disease (COPD) patients. Chest 2014; 145(3 Suppl):422A
27. Byers LA, Diao L, Wang J, et al. An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res 2013; 19(1):279-90
28. Toelle BG, Xuan W, Bird TE, et al. Respiratory symptoms and illness in older Australians: the burden of obstructive lung disease (BOLD) study. Med J Aust 2013; 198(3):144-8
29. Lung Foundation Australia. COPD: The statistics 2012. Available from: www. lungfoundation.com.au/professionalresources/statistics/copd-the-statistics/
30. COPD International. COPD Statistics. 2002. Available from: www.copdinternational. com/library/statistics.htm
31. CDC. Deaths from chronic obstructive pulmonary disease-United States. 2000MMWR Morb Mortal Wkly Rep 2008;57(45):1229-32
32. Hogg JC. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 2004;364(9435):709-21
33. Fletcher C, Peto R. The natural history of chronic bronchitis and emphysema. Postgrad Med J 1977;53(620):351
34. Sohal SS, Ward C, Danial W, et al. Recent advances in understanding inflammation and remodeling in the airways in chronic obstructive pulmonary disease. Expert Rev Respir Med 2013;7(3):275-88
35. Hogg JC, McDonough JE, Suzuki M. Small airway obstruction in COPD: new insights based on micro-CT imaging and MRI imaging. Chest 2013;143(5):1436-43
36. Yao H, Rahman I. Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease. Toxicol Appl Pharmacol 2011;254(2):72-85
37. Cosio MG, Saetta M, Agusti A. Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med 2009; 360(23):2445-54
38. Chung KF, Adcock IM. Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J 2008;31(6):1334-56
39. Perret JL, Dharmage SC, Matheson MC, et al. The interplay between the effects of lifetime asthma, smoking, and atopy on fixed airflow obstruction in middle age. Am J Respir Crit Care Med 2013;187(1):42-8
40. Matheson MC, Raven J, Johns DP, et al. Associations between reduced diffusing capacity and airflow obstruction in community-based subjects. Respir Med 2007;101(8):1730-7
41. National Heart, Lung, and and Blood Institute. Global initiative for chronic obstructive lung disease (GOLD). 2001
42. Walters EH, Walters J, Wills KE, et al. Clinical diaries in COPD: compliance and utility in predicting acute exacerbations. Int J Chron Obstruct Pulmon Dis 2012;7: 427-35
43. Walters JA, Walters EH, Nelson M, et al. Factors associated with misdiagnosis of COPD in primary care. Prim Care Respir J 2011;20(4):396-402
44. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009;119(6):1420-8
45. Soltani A, Muller HK, Sohal SS, et al. Distinctive characteristics of bronchial reticular basement membrane and vessel remodelling in chronic obstructive pulmonary disease (COPD) and in asthma: they are not the same disease. Histopathology 2012;60(6):964-70
46. Sohal SS, Reid D, Soltani A, et al. Evaluation of epithelial mesenchymal transition in patients with chronic obstructive pulmonary disease. Respir Res 2011;12:130
47. Sohal SS, Walters EH. Role of epithelial mesenchymal transition (EMT) in chronic obstructive pulmonary disease (COPD). Respir Res 2013;14(1):120
48. Sohal SS, Walters EH. Epithelial mesenchymal transition (EMT) in small airways of COPD patients. Thorax 2013; 68(8):783-4
49. Soltani A, Reid DW, Sohal SS, et al. Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study. Respir Res 2010;11:105
50. Wang Q, Wang Y, Zhang Y, et al. The role of uPAR in epithelial-mesenchymal transition in small airway epithelium of patients with chronic obstructive pulmonary disease. Respir Res 2013;14:67
51. Milara J, Peiró T, Serrano A, Cortijo J. Epithelial to mesenchymal transition is increased in patients with COPD and induced by cigarette smoke. Thorax 2013; 68(5):410-20
52. Camara J, Jarai G. Epithelial-mesenchymal transition in primary human bronchial epithelial cells is Smad-dependent and enhanced by fibronectin and TNF-alpha. Fibrogenesis Tissue Repair 2010;3(1):2
53. Hay ED. An overview of epithelio-mesenchymal transformation. Acta Anat (Basel) 1995;154(1):8-20
54. Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 2003; 112(12):1776-84
55. Iwano M, Plieth D, Danoff TM, et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 2002;110(3):341-50
56. Willis BC, Borok Z. TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease. Am J Physiol Lung Cell Mol Physiol 2007;293(3):L525-34
57. Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res 2009; 19(2):156-72
58. Kim MK, Maeng YI, Sung WJ, et al. The differential expression of TGF-beta1, ILK and wnt signaling inducing epithelial to mesenchymal transition in human renal fibrogenesis: an immunohistochemical study. Int J Clin Exp Pathol 2013;6(9):1747-58
59. Takizawa H, Tanaka M, Takami K, et al. Increased expression of transforming growth factor-beta1 in small airway epithelium from tobacco smokers and patients with chronic obstructive pulmonary disease (COPD). Am J Respir Crit Care Med 2001;163(6): 1476-83
60. Zhang M, Zhang Z, Pan HY, et al. TGF-beta1 induces human bronchial epithelial cell-to-mesenchymal transition in vitro. Lung 2009;187(3):187-94
61. Sime PJ, OReilly KM. Fibrosis of the lung and other tissues: new concepts in pathogenesis and treatment. Clin Immunol 2001;99(3):308-19
62. Fan JM, Ng YY, Hill PA, et al. Transforming growth factor-beta regulates tubular epithelial-myofibroblast transdifferentiation in vitro. Kidney Int 1999;56(4):1455-67
63. Kasai H, Allen JT, Mason RM, et al. TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT). Respir Res 2005;6:56
64. Kim KK, Kugler MC, Wolters PJ, et al. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci USA 2006;103(35):13180-5
65. Flanders KC. Smad3 as a mediator of the fibrotic response. Int J Exp Pathol 2004; 85(2):47-64
66. Miyazawa K, Shinozaki M, Hara T, et al. Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells 2002; 7(12):1191-204
67. Ju W, Ogawa A, Heyer J, et al. Deletion of Smad2 in mouse liver reveals novel functions in hepatocyte growth and differentiation. Mol Cell Biol 2006;26(2): 654-67
68. Zavadil J, Bottinger EP. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene 2005;24(37):5764-74
69. Tian F, DaCosta Byfield S, Parks WT, et al. Reduction in Smad2/3 signaling enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. Cancer Res 2003;63(23):8284-92
70. Bakin AV, Tomlinson AK, Bhowmick NA, et al. Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration. J Biol Chem 2000;275(47):36803-10
71. Lien SC, Usami S, Chien S, Chiu JJ. Phosphatidylinositol 3-kinase/Akt pathway is involved in transforming growth factor-beta1-induced phenotypic modulation of 10T1/2 cells to smooth muscle cells. Cell Signal 2006;18(8):1270-8
72. Kattla JJ, Carew RM, Heljic M, et al. Protein kinase B/Akt activity is involved in renal TGF-beta1-driven epithelial-mesenchymal transition in vitro and in vivo. Am J Physiol Renal Physiol 2008;295(1):F215-25
73. Zavadil J, Bitzer M, Liang D, et al. Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. Proc Natl Acad Sci USA 2001;98(12):6686-91
74. Rao VN, Reddy ES. elk-1 proteins interact with MAP kinases. Oncogene 1994;9(7): 1855-60
75. Boutet A, De Frutos CA, Maxwell PH, et al. Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney. EMBO J 2006;25(23): 5603-13
76. Dhasarathy A, Phadke D, Mav D, et al. The transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer. PLoS One 2011;6(10):e26514
77. Kang H, Lee M, Jang SW. Celastrol inhibits TGF-beta1-induced epithelial-mesenchymal transition by inhibiting Snail and regulating E-cadherin expression. Biochem Biophys Res Commun 2013;437(4):550-6
78. Medici D, Hay ED, Olsen BR. Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3. Mol Biol Cell 2008;19(11):4875-87
79. Yang J, Mani SA, Donaher JL, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 2004;117(7):927-39
80. Nusse R, Varmus H. Three decades of Wnts: a personal perspective on how a scientific field developed. EMBO J 2012; 31(12):2670-84
81. Woll PS, Morris JK, Painschab MS, et al. Wnt signaling promotes hematoendothelial cell development from human embryonic stem cells. Blood 2008;111(1):122-31
82. Angers S, Moon RT. Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol 2009;10(7):468-77
83. Sarkar FH, Li Y, Wang Z, Kong D. The role of nutraceuticals in the regulation of Wnt and Hedgehog signaling in cancer. Cancer Metastasis Rev 2010;29(3):383-94
84. Kim K, Lu Z, Hay ED. Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT. Cell Biol Int 2002;26(5):463-76
85. Fuxe J, Karlsson MC. TGF-beta-induced epithelial-mesenchymal transition: a link between cancer and inflammation. Semin Cancer Biol 2012;22(5-6):455-61
86. Yang L, Xie G, Fan Q, Xie J. Activation of the hedgehog-signaling pathway in human cancer and the clinical implications. Oncogene 2010;29(4):469-81
87. Hannigan G, Troussard AA, Dedhar S. Integrin-linked kinase: a cancer therapeutic target unique among its ILK. Nat Rev Cancer 2005;5(1):51-63
88. Chen D, Zhang Y, Zhang X, et al. Overexpression of integrin-linked kinase correlates with malignant phenotype in non-small cell lung cancer and promotes lung cancer cell invasion and migration via regulating epithelial-mesenchymal transition (EMT)-related genes. Acta Histochem 2013; 115(2):128-36
89. Margadant C, Sonnenberg A. Integrin-TGF-beta crosstalk in fibrosis, cancer and wound healing. EMBO Rep 2010;11(2):97-105
90. Chandrasekar N, Mohanam S, Gujrati M, et al. Downregulation of uPA inhibits migration and PI3k/Akt signaling in glioblastoma cells. Oncogene 2003;22(3): 392-400
91. Jo M, Lester RD, Montel V, et al. Reversibility of epithelial-mesenchymal transition (EMT) induced in breast cancer cells by activation of urokinase receptor-dependent cell signaling. J Biol Chem 2009;284(34):22825-33
92. Lester RD, Jo M, Montel V, et al. uPAR induces epithelial-mesenchymal transition in hypoxic breast cancer cells. J Cell Biol 2007;178(3):425-36
93. Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3 kinase/AKT pathways. Oncogene 2005;24(50):7443-54
94. Vignola AM, Chanez P, Chiappara G, et al. Transforming growth factor-beta expression in mucosal biopsies in asthma and chronic bronchitis. Am J Respir Crit Care Med 1997;156(2 Pt 1):591-9
95. Soltani A, Sohal SS, Reid D, et al. Vessel-associated transforming growth factor-beta1 (TGF-beta1) is increased in the bronchial reticular basement membrane in COPD and normal smokers. PLoS One 2012;7(6):e39736