Lipopolysaccharide enhances mouse lung tumorigenesis: a model for inflammation-driven lung cancer

Vet Pathol. 2013 Sep;50(5):895-902. doi: 10.1177/0300985813476061. Epub 2013 Feb 4.


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.

Keywords: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; animal model; lipopolysaccharide; lung tumor; macrophage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Blotting, Western
  • Carcinogenesis / drug effects*
  • Disease Models, Animal*
  • Immunohistochemistry
  • Linear Models
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / adverse effects*
  • Lung Neoplasms / chemically induced*
  • Lung Neoplasms / physiopathology*
  • Mice
  • Nitrosamines / adverse effects*


  • Lipopolysaccharides
  • Nitrosamines
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone