Lipopolysaccharide Enhances Mouse Lung Tumorigenesis: A Model for Inflammation-Driven Lung Cancer

T. Melkamu, X. Qian, P. Upadhyaya, M. G. O'Sullivan, F. Kassie

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)895-902
Number of pages8
JournalVeterinary pathology
Volume50
Issue number5
DOIs
StatePublished - Sep 1 2013

Keywords

  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
  • animal model
  • lipopolysaccharide
  • lung tumor
  • macrophage

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