Ethanol Supports Macrophage Recruitment and Reinforces Invasion and Migration of L ewis Lung Carcinoma

Background Inflammation plays a critical role in cancer progression, and our data suggested that ethanol ( E t OH ) could promote the progression of breast cancer via increased monocyte chemo‐attractant protein‐1 ( MCP ‐1). Thus, we investigated the effects of E t OH on lung cancer growth and metastasis to explore whether immunosuppression had a role. Methods C 57 BL /6 mice ( n  = 10) implanted with L ewis lung cancer ( LLC ) cells were used to model physiologically relevant E t OH intake on tumor growth and inflammation after macrophage polarization. Tumors were isolated and measured, and MCP ‐1 expression was measured via immunohistochemistry and W estern blot. Recruitment of macrophages using CD 11b and F 4/80 antibodies was detected with immunohistochemistry and flow cytometry. Changes in arginase I and inducible nitric oxide synthase (iNOS) expression were measured with immunofluorescent microscopy. E t OH 's effect on in vitro tumor angiogenesis was evaluated in culture, and the tumor microvessel density was assessed with CD 31 immunohistochemistry. Matrix metalloproteinase 9 and interleukin 10 expressions were measured by W estern blot, ELISA , and immunohistochemistry. Finally, we treated a macrophage cell line RAW 264.7 with E t OH and measured changes in arginase I and i NOS expression. Results With E t OH exposure, macrophage density was positively correlated with MCP ‐1 expression. Macrophages infiltrated the tumor site, becoming tumor‐associated macrophages that polarized to M 2 phenotypes ( A rgI high /i NOS low ) after E t OH treatment. Cancerous cells interacted with immune cells, especially M 2 macrophages, and promoted tumor angiogenesis, progression, and invasiveness. RAW 264.7 cells stimulated with E t OH expressed more arginase I and less i NOS than controls. These results agreed with the features of M 2 phenotype macrophages ( A rgI high /i NOS low ). Conclusions Data show that E t OH induced M 2 phenotype macrophages, suggesting that progression and metastasis of LLC may be mediated by recruitment of M 2 macrophages, especially under the influence of E t OH .