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Open Access 01-12-2010 | Research

Allergic inflammation does not impact chemical-induced carcinogenesis in the lungs of mice

Authors: Konstantinos Doris, Sophia P Karabela, Chrysoula A Kairi, Davina CM Simoes, Charis Roussos, Spyros G Zakynthinos, Ioannis Kalomenidis, Timothy S Blackwell, Georgios T Stathopoulos

Published in: Respiratory Research | Issue 1/2010

Abstract

Background

Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice.

Methods

Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment.

Results

Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis.

Conclusions

Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2008. CA Cancer J Clin 2008, 58:71–96.CrossRefPubMed

Doll R, Peto R: Cigarette smoking and bronchial carcinoma: dose and time relationships among regular smokers and lifelong non-smokers. J Epidemiol Commun Health 1978, 32:303–313.CrossRef

Peto R, Lopez AD, Boreham J, Thun M: [http://www.ctsu.ox.ac.uk/~tobacco] Mortality from Smoking in Developed Countries 1950–2000. Oxford: Oxford University Press; 2006.

Subramanian J, Govindan R: Molecular genetics of lung cancer in people who have never smoked. Lancet Oncol 2008, 9:676–682.CrossRefPubMed

Sun S, Schiller JH, Gazdar AF: Lung cancer in never smokers-a different disease. Nat Rev Cancer 2007, 7:778–790.CrossRefPubMed

International Early Lung Cancer Action Program Investigators, Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS: Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006, 355:1763–1771.CrossRef

Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y: NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 2004, 431:461–466.CrossRefPubMed

Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M: IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004, 118:285–296.CrossRefPubMed

Stathopoulos GT, Sherrill TP, Cheng DS, Scoggins RM, Han W, Polosukhin VV, Connelly L, Yull FE, Fingleton B, Blackwell TS: Epithelial Nuclear Factor-κB Activation Promotes Urethane-Induced Lung Carcinogenesis. Proc Natl Acad Sci USA 2007, 104:18514–18519.CrossRefPubMedPubMedCentral

10.

Meylan E, Dooley AL, Feldser DM, Shen L, Turk E, Ouyang C, Jacks T: Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma. Nature 2009, 462:104–107.CrossRefPubMedPubMedCentral

11.

Takahashi H, Ogata H, Nishigaki R, Broide DH, Karin M: Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation. Cancer Cell 2010, 17:89–97.CrossRefPubMedPubMedCentral

12.

Thiberville L, Salaün M, Lachkar S, Dominique S, Moreno-Swirc S, Vever-Bizet C, Bourg-Heckly G: Human in vivo fluorescence microimaging of the alveolar ducts and sacs during bronchoscopy. Eur Respir J 2009, 33:974–985.CrossRefPubMed

13.

Burgel PR, Nadel JA: Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases. Eur Respir J 2008, 32:1068–1081.CrossRefPubMed

14.

Curtis JL, Freeman CM, Hogg JC: The Immunopathogenesis of Chronic Obstructive Pulmonary Disease. Insights from Recent Research. Proc Am Thorac Soc 2007, 4:512–521.CrossRefPubMedPubMedCentral

15.

Hogg JC: Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 2004, 364:709–721.CrossRefPubMed

16.

Boffetta P, Ye W, Boman G, Nyrén O: Lung cancer risk in a population-based cohort of patients hospitalized for asthma in Sweden. Eur Respir J 2002, 19:127–133.CrossRefPubMed

17.

Santillan AA, Camargo CA Jr, Colditz GA: A meta-analysis of asthma and risk of lung cancer (United States). Cancer Causes Control 2003, 14:327–334.CrossRefPubMed

18.

Brown DW, Young KE, Anda RF, Felitti VJ, Giles WH: Re: asthma and the risk of lung cancer. findings from the Adverse Childhood Experiences (ACE). Cancer Causes Control 2006, 17:349–350.CrossRefPubMed

19.

Seow A, Ng DP, Choo S, Eng P, Poh WT, Ming T, Wang YT: Joint effect of asthma/atopy and an IL-6 gene polymorphism on lung cancer risk among lifetime non-smoking Chinese women. Carcinogenesis 2006, 27:1240–1244.CrossRefPubMed

20.

Brown DW, Young KE, Anda RF, Giles WH: Asthma and risk of death from lung cancer: NHANES II Mortality Study. J Asthma 2005, 42:597–600.CrossRefPubMed

21.

Xanthou G, Alissafi T, Semitekolou M, Simoes DC, Economidou E, Gaga M, Lambrecht BN, Lloyd CM, Panoutsakopoulou V: Osteopontin has a crucial role in allergic airway disease through regulation of dendritic cell subsets. Nat Med 2007, 13:570–578.CrossRefPubMedPubMedCentral

22.

Lloyd CM: Building better mouse models of asthma. Curr Allergy Asthma Rep 2007, 7:231–236.CrossRefPubMedPubMedCentral

23.

Simoes DC, Xanthou G, Petrochilou K, Panoutsakopoulou V, Roussos C, Gratziou C: Osteopontin deficiency protects against airway remodeling and hyper-responsiveness in chronic asthma. Am J Respir Crit Care Med 2009, 179:894–902.CrossRefPubMed

24.

Malkinson AM: Primary lung tumors in mice: an experimentally manipulable model of human adenocarcinoma. Cancer Res 1992, 52:2670s-2676s.PubMed

25.

Malkinson AM: Molecular comparison of human and mouse pulmonary adenocarcinomas. Exp Lung Res 1998, 24:541–555.CrossRefPubMed

26.

Malkinson AM: Primary lung tumors in mice as an aid for understanding, preventing, and treating human adenocarcinoma of the lung. Lung Cancer 2001, 32:265–279.CrossRefPubMed

27.

Kopf M, Brombacher F, Hodgkin PD, Ramsay AJ, Milbourne EA, Dai WJ, Ovington KS, Behm CA, Köhler G, Young IG, Matthaei KI: IL-5-deficient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity 1996, 4:15–24.CrossRefPubMed

28.

Miller YE, Dwyer-Nield LD, Keith RL, Le M, Franklin WA, Malkinson AM: Induction of a high incidence of lung tumors in C57BL/6 mice with multiple ethyl carbamate injections. Cancer Letters 2003, 198:139–144.CrossRefPubMed

29.

Bernert H, Sekikawa K, Radcliffe RA, Iraqi F, You M, Malkinson AM: Tnfa and Il-10 deficiencies have contrasting effects on lung tumor susceptibility: gender-dependent modulation of IL-10 haploinsufficiency. Mol Carcinog 2003, 38:117–123.CrossRefPubMed

30.

Holgate ST, Polosa R: Treatment strategies for allergy and asthma. Nat Rev Immunol 2008, 8:218–230.CrossRefPubMed

31.

Hecht SS: Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst 1999, 91:1194–1210.CrossRefPubMed

32.

Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J: Global Initiative for Chronic Obstructive Lung Disease: global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007, 176:532–555.CrossRefPubMed

33.

Houghton AM, Mouded M, Shapiro SD: Common origins of lung cancer and COPD. Nat Med 2008, 14:1023–1024.CrossRefPubMed

34.

Tockman MS, Anthonisen NR, Wright EC, Donithan MG: Airways obstruction and the risk for lung cancer. Ann Intern Med 1987, 106:512–518.CrossRefPubMed

35.

Skillrud DM, Offord KP, Miller RD: Higher risk of lung cancer in chronic obstructive pulmonary disease: a prospective, matched, controlled study. Ann Intern Med 1986, 105:503–507.CrossRefPubMed

36.

Alberg AJ, Ford JG, Samet JM, American College of Chest Physicians: Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines. Chest 2nd edition. 2007, 132:29S-55S.CrossRefPubMed

37.

Alberg AJ, Samet JM: Epidemiology of lung cancer. Chest 2003, 123:21S-49S.CrossRefPubMed

38.

The Global Strategy for Asthma Management and Prevention (GINA) [http://www.ginasthma.com/]

39.

Stathopoulos GT, Sherrill TP, Karabela SP, Goleniewska K, Kalomenidis I, Roussos C, Fingleton B, Yull FE, Peebles RS Jr, Blackwell TS: Host-derived interleukin-5 promotes adenocarcinoma-induced malignant pleural effusion. Am J Respir Crit Care Med 2010, in press. PMID: 20595227.

40.

Moghaddam SJ, Li H, Cho SN, Dishop MK, Wistuba II, Ji L, Kurie JM, Dickey BF, DeMayo FJ: Promotion of Lung Carcinogenesis by Chronic Obstructive Pulmonary Disease-Like Airway Inflammation in a K-ras-Induced Mouse Model. Am J Respir Cell Mol Biol 2009, 40:443–453.CrossRefPubMed

41.

Wahl LM, Kleinman HK: Tumor-associated macrophages as targets for cancer therapy. J Natl Cancer Inst 1998, 90:1583–1584.CrossRefPubMed

42.

Mantovani A: The yin-yang of tumor-associated neutrophils. Cancer Cell 2009, 16:173–174.CrossRefPubMed

43.

Cormier SA, Taranova AG, Bedient C, Nguyen T, Protheroe C, Pero R, Dimina D, Ochkur SI, O'Neill K, Colbert D, Lombari TR, Constant S, McGarry MP, Lee JJ, Lee NA: Pivotal Advance: eosinophil infiltration of solid tumors is an early and persistent inflammatory host response. J Leukoc Biol 2006, 79:1131–1139.CrossRefPubMedPubMedCentral

44.

Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, Major ML, Gusarova GA, Yoder HM, Costa RH, Kalinichenko VV: The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res 2006, 66:2153–2161.CrossRefPubMed

45.

Sridharan L, Greenland P: Editorial policies and publication bias: the importance of negative studies. Arch Intern Med 2009, 169:1022–1023.CrossRefPubMed

46.

de Abreu MG: Negative studies deserve more attention. Am J Respir Crit Care Med 2006, 173:1414–1415.CrossRefPubMed

Title: Allergic inflammation does not impact chemical-induced carcinogenesis in the lungs of mice
Authors: Konstantinos Doris
Sophia P Karabela
Chrysoula A Kairi
Davina CM Simoes
Charis Roussos
Spyros G Zakynthinos
Ioannis Kalomenidis
Timothy S Blackwell
Georgios T Stathopoulos
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Respiratory Research / Issue 1/2010
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/1465-9921-11-118

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