Macrophages promote proliferation of lung cancer cell by activation of NFκB

Tumor-associated macrophages (TAMs) have been shown to promote tumor development including the growth, survival, invasion and metastasis of tumor cells. Cigarette smoke is a risk factor for a number of lung diseases including carcinogenesis, chronic obstructive pulmonary disease (COPD) by inducing an inflammatory response in the lung. Clinical studies have shown that patients with lung cancer who stop smoking have longer survival rate compared to patients who continue to smoke. The aim of the study was to demonstrate if macrophages promote proliferation of lung cancer cell and whether NF-κB activation is responsible for this process. To determine macrophages impact on lung cancer cells, the transwell inserts were used in co-culture model. We investigated the effects of macrophages on the proliferation and apoptosis of lung cancer cell lines (A549, U1810). Furthermore we analyzed whether exposure to cigarette smoke extract (CSE) enhances this effect. After 4 days co-culture, our results show that co-culture of macrophages and A549 cells significantly promotes the proliferation of lung cancer cells as measured by ELISA(5-bromodeoxyuridine, BrdU label) and FACS (carboxyfluorescein succinimidyl ester, CFSE label) analysis. Exposure of macrophages together with 0.5% CSE resulted in increased proliferation of A549 cells. CSE-enhanced proliferation was cell type-specific, as CSE exposure could not enhance proliferation of U1810 cells in co-culture with macrophages. Increased activation of NF-κB was observed in both macrophages and A549 cells in co-culture or after exposure of CSE. The proliferation of A549 cells were blocked by the NF-κB inhibitor BAY 11–7082. In conclusion, our results indicate that macrophages promote the growth of lung cancer cells. This effect is increased by CSE due to the activation of NF-κB. These results could contribute to the poor therapeutic effect to patients with lung cancer who smoke during cancer therapy.