title: Lipopolysaccharide enhances mouse lung tumorigenesis: a model for inflammation-driven lung cancer.
abstract: The association between pulmonary inflammation and lung cancer is well established. However, currently there are no appropriate models that recapitulate inflammation-related lung cancer in humans. In the present study, we examined, in 2 tumor bioassays, enhancement by bacterial lipopolysaccharide (LPS) of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. Mice that were treated with NNK alone developed 29.6 ± 9.8 and 36.2 ± 4.1 lung tumors per mouse in experiments 1 and 2, respectively. Chronic intranasal instillation of LPS to NNK-treated mice increased the multiplicity of lung tumors to 47.3 ± 16.1 and 51.2 ± 4.8 lung tumors per mouse in experiments 1 and 2, corresponding to a significant increase by 60% and 41%, respectively. Moreover, administration of LPS to NNK-pretreated mice significantly increased the multiplicity of larger tumors and histopathologically more advanced lesions (adenoma with dysplasia and adenocarcinoma), macrophage recruitment to the peritumoral area, and expression of inflammation-, cell proliferation-, and survival-related proteins. Overall, our findings demonstrated the promise of the NNK-LPS-A/J mice model to better understand inflammation-driven lung cancer, dissect the molecular pathways involved, and identify more effective preventive and therapeutic agents against lung cancer.
authors: Masonic Cancer Center, University of Minnesota, Mayo Mail Code 806, 420 Delaware Street SE, Minneapolis, MN 55455. Email: kassi012@umn.edu.
authors: T
authors: T
authors: Melkamu
authors: X
authors: X
authors: Qian
authors: P
authors: P
authors: Upadhyaya
authors: M G
authors: MG
authors: O'Sullivan
authors: F
authors: F
authors: Kassie
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D015153:Blotting, Western; D063646:Carcinogenesis / Q000187:drug effects*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D016014:Linear Models; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects*; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000503:physiopathology*; D051379:Mice; D009602:Nitrosamines / Q000009:adverse effects*
chemical_list: D008070:Lipopolysaccharides; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
keywords: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; animal model; lipopolysaccharide; lung tumor; macrophage
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