Mucins in lung cancer: Diagnostic, prognostic, and therapeutic implications

Journal of Thoracic Oncology

Volumn 10, Issue 1, 2015, Pages 19-27

  Lakshmanan, Imayavaramban ^a   Ponnusamy, Moorthy P ^a   Macha, Muzafar A ^a   Haridas, Dhanya ^a   Majhi, Prabin Dhangada ^a   Kaur, Sukhwinder ^a   Jain, Maneesh ^a   Batra, Surinder K ^a   Ganti, Apar Kishor ^a,b  

^a VA NEBRASKA WESTERN IOWA HEALTH CARE SYSTEM   (United States)

^b UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

Aptamer; L BLP25; Lung cancer; MUC1; MUC4; MUC5AC; MUC7; Mucin vaccines; Mucins; TG4010

Indexed keywords

MUCIN; MUCIN 1; MUCIN 2; MUCIN 4; MUCIN 5AC; MUCIN 5B; MUCIN 6; MUCIN 7; TG 4010;

CANCER IMMUNOTHERAPY; CANCER PATIENT; DRUG TARGETING; HUMAN; LUNG ALVEOLUS EPITHELIUM; LUNG CANCER; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; DISEASE COURSE; IMMUNOHISTOCHEMISTRY; LUNG NEOPLASMS; METABOLISM; PROGNOSIS;

DISEASE PROGRESSION; HUMANS; IMMUNOHISTOCHEMISTRY; LUNG NEOPLASMS; MUCINS; PROGNOSIS;

EID: 84926421581     PISSN: 15560864     EISSN: 15561380     Source Type: Journal    
DOI: 10.1097/JTO.0000000000000404     Document Type: Review

References (75)

1. Van Klinken BJ, Einerhand AW, Buller HA, Dekker J. Strategic biochemical analysis of mucins. Anal Biochem 1998;265:103-116.
2. Kufe DW. Mucins in cancer: Function, prognosis and therapy. Nat Rev Cancer 2009;9:874-885.
3. Awaya H, Takeshima Y, Yamasaki M, Inai K. Expression of MUC1, MUC2, MUC5AC, and MUC6 in atypical adenomatous hyperplasia, bronchioloalveolar carcinoma, adenocarcinoma with mixed subtypes, and mucinous bronchioloalveolar carcinoma of the lung. Am J Clin Pathol 2004;121:644-653.
4. Hanaoka J, Kontani K, Sawai S, et al. Analysis of MUC4 mucin expression in lung carcinoma cells and its immunogenicity. Cancer 2001;92:2148-2157.
5. Kaira K, Okumura T, Nakagawa K, et al. MUC1 expression in pulmonary metastatic tumors: A comparison of primary lung cancer. Pathol Oncol Res 2012;18:439-447.
6. Kwon KY, Ro JY, Singhal N, et al. MUC4 expression in non-small cell lung carcinomas: Relationship to tumor histology and patient survival. Arch Pathol Lab Med 2007;131:593-598.
7. Hollingsworth MA, Swanson BJ. Mucins in cancer: Protection and control of the cell surface. Nat Rev Cancer 2004;4:45-60.
8. Gao J, McConnell MJ, Yu B, et al. MUC1 is a downstream target of STAT3 and regulates lung cancer cell survival and invasion. Int J Oncol 2009;35:337-345.
9. Kim KC, Lillehoj EP. MUC1 mucin: A peacemaker in the lung. Am J Respir Cell Mol Biol 2008;39:644-647.
10. Lakshmanan I, Ponnusamy MP, Das S, et al. MUC16 induced rapid G2/M transition via interactions with JAK2 for increased proliferation and anti-apoptosis in breast cancer cells. Oncogene 2012;31:805-817.
11. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9-29.
12. Rose MC. Mucins: Structure, function, and role in pulmonary diseases. Am J Physiol 1992;263:L413-L429.
13. Buisine MP, Devisme L, Copin MC, et al. Developmental mucin gene expression in the human respiratory tract. Am J Respir Cell Mol Biol 1999;20:209-218.
14. Perrais M, Pigny P, Copin MC, Aubert JP, Van Seuningen I. Induction of MUC2 and MUC5AC mucins by factors of the epidermal growth factor (EGF) family is mediated by EGF receptor/Ras/Raf/extracellular signal-regulated kinase cascade and Sp1. J Biol Chem 2002;277:32258-32267.
15. Copin MC, Devisme L, Buisine MP, et al. From normal respiratory mucosa to epidermoid carcinoma: Expression of human mucin genes. Int J Cancer 2000;86:162-168.
16. Roy MG, Rahmani M, Hernandez JR, et al. Mucin production during prenatal and postnatal murine lung development. Am J Respir Cell Mol Biol 2011;44:755-760.
17. Hilkens J, Ligtenberg MJ, Vos HL, Litvinov SV. Cell membrane-associated mucins and their adhesion-modulating property. Trends Biochem Sci 1992;17:359-363.
18. Nath S, Mukherjee P. MUC1: A multifaceted oncoprotein with a key role in cancer progression. Trends Mol Med 2014;20:332-342.
19. Kaira K, Nakagawa K, Ohde Y, et al. Depolarized MUC1 expression is closely associated with hypoxic markers and poor outcome in resected non-small cell lung cancer. Int J Surg Pathol 2012;20:223-232.
20. Jarrard JA, Linnoila RI, Lee H, Steinberg SM, Witschi H, Szabo E. MUC1 is a novel marker for the type II pneumocyte lineage during lung carcinogenesis. Cancer Res 1998;58:5582-5589.
21. Guddo F, Giatromanolaki A, Patriarca C, et al. Depolarized expression of episialin (EMA, MUC1) in lung adenocarcinoma is associated with tumor progression. Anticancer Res 1998;18:1915-1920.
22. Nagai S, Takenaka K, Sonobe M, Ogawa E, Wada H, Tanaka F. A novel classification of MUC1 expression is correlated with tumor differentiation and postoperative prognosis in non-small cell lung cancer. J Thorac Oncol 2006;1:46-51.
23. Giatromanolaki A, Koukourakis MI, Sivridis E, et al. Coexpression of MUC1 glycoprotein with multiple angiogenic factors in non-small cell lung cancer suggests coactivation of angiogenic and migration pathways. Clin Cancer Res 2000;6:1917-1921.
24. Makiguchi Y, Hinoda Y, Imai K. Effect of MUC1 mucin, an anti-adhesion molecule, on tumor cell growth. Jpn J Cancer Res 1996;87:505-511.
25. Mikami Y, Hisatsune A, Tashiro T, Isohama Y, Katsuki H. Hypoxia enhances MUC1 expression in a lung adenocarcinoma cell line. Biochem Biophys Res Commun 2009;379:1060-1065.
26. Pochampalli MR, el Bejjani RM, Schroeder JA. MUC1 is a novel regulator of ErbB1 receptor trafficking. Oncogene 2007;26:1693-1701.
27. Li Y, Ren J, Yu W, et al. The epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin. J Biol Chem 2001;276:35239-35242.
28. Bitler BG, Menzl I, Huerta CL, et al. Intracellular MUC1 peptides inhibit cancer progression. Clin Cancer Res 2009;15:100-109.
29. Klinge CM, Radde BN, Imbert-Fernandez Y, et al. Targeting the intracellular MUC1 C-terminal domain inhibits proliferation and estrogen receptor transcriptional activity in lung adenocarcinoma cells. Mol Cancer Ther 2011;10:2062-2071.
30. Ramasamy S, Duraisamy S, Barbashov S, Kawano T, Kharbanda S, Kufe D. The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop. Mol Cell 2007;27:992-1004.
31. Raina D, Kharbanda S, Kufe D. The MUC1 oncoprotein activates the anti-apoptotic phosphoinositide 3-kinase/Akt and Bcl-xL pathways in rat 3Y1 fibroblasts. J Biol Chem 2004;279:20607-20612.
32. Raina D, Kosugi M, Ahmad R, et al. Dependence on the MUC1-C oncoprotein in non-small cell lung cancer cells. Mol Cancer Ther 2011;10:806-816.
33. Kuwahara I, Lillehoj EP, Hisatsune A, et al. Neutrophil elastase stimulates MUC1 gene expression through increased Sp1 binding to the MUC1 promoter. Am J Physiol Lung Cell Mol Physiol 2005;289:L355-L362.
34. Molina-Pinelo S, Gutiérrez G, Pastor MD, et al. MicroRNA-dependent regulation of transcription in non-small cell lung cancer. PLoS One 2014;9:e90524.
35. Bansil R, Stanley E, LaMont JT. Mucin biophysics. Annu Rev Physiol 1995;57:635-657.
36. Llinares K, Escande F, Aubert S, et al. Diagnostic value of MUC4 immunostaining in distinguishing epithelial mesothelioma and lung adenocarcinoma. Mod Pathol 2004;17:150-157.
37. Karg A, Dinç ZA, Başok O, Uçvet A. MUC4 expression and its relation to ErbB2 expression, apoptosis, proliferation, differentiation, and tumor stage in non-small cell lung cancer (NSCLC). Pathol Res Pract 2006;202:577-583.
38. Tsutsumida H, Goto M, Kitajima S, et al. MUC4 expression correlates with poor prognosis in small-sized lung adenocarcinoma. Lung Cancer 2007;55:195-203.
39. Majhi PD, Lakshmanan I, Ponnusamy MP, et al. Pathobiological implications of MUC4 in non-small-cell lung cancer. J Thorac Oncol 2013;8:398-407.
40. Damera G, Xia B, Ancha HR, Sachdev GP. IL-9 modulated MUC4 gene and glycoprotein expression in airway epithelial cells. Biosci Rep 2006;26:55-67.
41. Yamada N, Nishida Y, Tsutsumida H, et al. Promoter CpG methylation in cancer cells contributes to the regulation of MUC4. Br J Cancer 2009;100:344-351.
42. Barsky SH, Cameron R, Osann KE, Tomita D, Holmes EC. Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features. Cancer 1994;73:1163-1170.
43. Kim S, Lewis C, Nadel JA. CCL20/CCR6 feedback exaggerates epidermal growth factor receptor-dependent MUC5AC mucin production in human airway epithelial (NCI-H292) cells. J Immunol 2011;186:3392-3400.
44. Kang JH, Lee EH, Park SW, Chung IY. MUC5AC expression through bidirectional communication of Notch and epidermal growth factor receptor pathways. J Immunol 2011;187:222-229.
45. Chen Y, Watson AM, Williamson CD, et al. Glucocorticoid receptor and histone deacetylase-2 mediate dexamethasone-induced repression of MUC5AC gene expression. Am J Respir Cell Mol Biol 2012;47:637-644.
46. Chen Y, Zhao YH, Di YP, Wu R. Characterization of human mucin 5B gene expression in airway epithelium and the genomic clone of the amino-terminal and 5′-flanking region. Am J Respir Cell Mol Biol 2001;25:542-553.
47. Iwashita J, Yamamoto T, Sasaki Y, Abe T. MUC5AC production is down-regulated in NCI-H292 lung cancer cells cultured on type-IV collagen. Mol Cell Biochem 2010;337:65-75.
48. Bai CH, Song SY, Kim YD. The inhibitory effect of the leukotriene receptor antagonist on leukotriene D4-induced MUC2/5AC gene expression and mucin secretion in human airway epithelial cells. Auris Nasus Larynx 2007;34:203-206.
49. Skrzypek K, Tertil M, Golda S, et al. Interplay between heme oxygenase-1 and miR-378 affects non-small cell lung carcinoma growth, vascularization, and metastasis. Antioxid Redox Signal 2013;19:644-660.
50. Hamamoto A, Abe Y, Nishi M, et al. Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts. Int J Oncol 2005;26:891-896.
51. Rossi G, Murer B, Cavazza A, et al. Primary mucinous (so-called colloid) carcinomas of the lung: A clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression. Am J Surg Pathol 2004;28:442-452.
52. Fan H, Bobek LA. Regulation of human MUC7 mucin gene expression by cigarette smoke extract or cigarette smoke and Pseudomonas aeruginosa lipopolysaccharide in human airway epithelial cells and in MUC7 transgenic mice. Open Respir Med J 2010;4:63-70.
53. Situ D, Wang J, Ma Y, et al. Expression and prognostic relevance of MUC1 in stage IB non-small cell lung cancer. Med Oncol 2011;28:S596-S604.
54. Demirag F, Cakir E, Bayiz H, Eren Yazici U. MUC1 and bcl-2 expression in preinvasive lesions and adenosquamous carcinoma of the lung. Acta Chir Belg 2013;113:19-24.
55. Powell E, Chow LQ. BLP-25 liposomal vaccine: A promising potential therapy in non-small-cell lung cancer. Expert Rev Respir Med 2008;2:37-45.
56. Spira A, Beane J, Shah V, et al. Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci USA 2004;101:10143-10148.
57. Khodarev NN, Pitroda SP, Beckett MA, et al. MUC1-induced transcriptional programs associated with tumorigenesis predict outcome in breast and lung cancer. Cancer Res 2009;69:2833-2837.
58. MacDermed DM, Khodarev NN, Pitroda SP, et al. MUC1-associated proliferation signature predicts outcomes in lung adenocarcinoma patients. BMC Med Genomics 2010;3:16.
59. Ohnishi H, Yokoyama A, Kondo K, et al. Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med 2002;165:378-381.
60. Shields PG. Molecular epidemiology of lung cancer. Ann Oncol 1999;10:S7-11.
61. Matsumura N, Yamamoto M, Aruga A, Takasaki K, Nakano M. Correlation between expression of MUC1 core protein and outcome after surgery in massforming intrahepatic cholangiocarcinoma. Cancer 2002;94:1770-1776.
62. Weed DT, Gomez-Fernandez C, Bonfante E, et al. MUC4 (sialomucin complex) expression in salivary gland tumors and squamous cell carcinoma of the upper aerodigestive tract. Otolaryngol Head Neck Surg 2001;124:127-141.
63. Gao L, Liu J, Zhang B, et al. Functional MUC4 suppress epithelial-mesenchymal transition in lung adenocarcinoma metastasis. Tumour Biol 2001;35:1335-1341.
64. Hishida T, Ishii G, Kodama T, et al. Centrally located adenocarcinoma with endobronchial polypoid growth: Clinicopathological analysis of five cases. Pathol Int 2011;61:73-79.
65. Yu CJ, Shih JY, Lee YC, Shun CT, Yuan A, Yang PC. Sialyl Lewis antigens: Association with MUC5AC protein and correlation with post-operative recurrence of non-small cell lung cancer. Lung Cancer 2005;47:59-67.
66. López-Ferrer A, Curull V, Barranco C, et al. Mucins as differentiation markers in bronchial epithelium. Squamous cell carcinoma and adenocarcinoma display similar expression patterns. Am J Respir Cell Mol Biol 2001;24:22-29.
67. Szabo E. MUC1 expression in lung cancer. Methods Mol Med 2003;74:251-258.
68. Sangha R, Butts C. L-BLP25: A peptide vaccine strategy in non small cell lung cancer. Clin Cancer Res 2007;13:s4652-s4654.
69. Butts C, Murray N, Maksymiuk A, et al. Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. J Clin Oncol 2005;23:6674-6681.
70. Brossart P, Heinrich KS, Stuhler G, et al. Identification of HLA-A2-restricted T-cell epitopes derived from the MUC1 tumor antigen for broadly applicable vaccine therapies. Blood 1999;93:4309-4317.
71. Sharpe JC, Abel PD, Gilbertson JA, et al. Modulated expression of human leucocyte antigen class I and class II determinants in hyperplastic and malignant human prostatic epithelium. Br J Urol 1994;74:609-616.
72. Wu YL, Park K, Soo RA, et al. INSPIRE: A phase III study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stage III non-small cell lung cancer. BMC Cancer 2011;11:430.
73. Ramlau R, Quoix E, Rolski J, et al. A phase II study of Tg4010 (Mva-Muc1-Il2) in association with chemotherapy in patients with stage III/IV non-small cell lung cancer. J Thorac Oncol 2008;3:735-744.
74. Kurosaki T, Higuchi N, Kawakami S, et al. Self-assemble gene delivery system for molecular targeting using nucleic acid aptamer. Gene 2012;491:205-209.
75. Rahn JJ, Dabbagh L, Pasdar M, Hugh JC. The importance of MUC1 cellular localization in patients with breast carcinoma: An immunohistologic study of 71 patients and review of the literature. Cancer 2001;91:1973-1982.