COPD-like inflammation drives the progression of K-ras induced early cancerous lesions

Background Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer (LC). COPD is characterized by chronic inflammation of the airways and lung infections. Adenocarcinomas are frequently associated with an activating mutation in the K-ras gene. The aim of this study was to determine the effect of COPD-like inflammation on the progression of K-ras induced cancerous lesions. Methods Mice were exposed to cigarette smoke (CS) 5 days/week. CS- or air exposed mice were exposed to a clinical isolate of heat inactivated non-typeable Haemophilus influenzae (NTHi) 3 days/week. Histologic analysis were performed on formalin fixed and paraffin embedded sections. Pre-cancerous lesions were divided into alveolar hyperplasia (AH), alveolar adenomatous hyperplasia (AAH), and adenocarcinoma. AH were defined by an increase of cells along the interalveolar septa in the alveolar space. AH developed from single-layered lesions into AAH, characterized by a further increase in cellularity. The structure of the alveoli was recognizable, without invasive growth. Cells within adenocarcinoma were charcterized by a round shape, nuclear atypia and less differentiation compared to AH. Results Mice with an oncogenic K-ras allele in lung epithelium were exposed to CS, NTHi, and the combination of CS and NTHi for 12 weeks. Exposure of mice to NTHi resulted in an increased total burden and in increased numbers of AAH lesions, whereas exposure to CS alone did not affect tumor growth. Combined exposure to CS and NTHi led to larger pre-cancerous lesions and an increased adenocarcinoma formation. Conclusions CS and NTHi promote the progression of K-ras induced early cancerous lesions resulting in more severe phenotype.