Lipopolysaccharide enhances mouse lung tumorigenesis: a model for inflammation-driven lung cancer.
Lipopolysaccharide enhances mouse lung tumorigenesis: a model for inflammation-driven lung cancer.
复制标题
DOI：
10.1177/0300985813476061
复制
发表时间：
2013-09
影响因子：
2.4
通讯作者：
Kassie F
中科院分区：
文献类型：
--
作者：
Melkamu T;Qian X;Upadhyaya P;O'Sullivan MG;Kassie F
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 two 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/mouse in experiment 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/mouse in experiment 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.
