Abstract 451: Macrophages are critical for promotion of urethane-induced lung carcinogenesis during early stages

Abstract

Abstract Among the multiple factors initiating and supporting tumor growth, inflammation plays one of the most important roles. Macrophages, which are the primary immune cells in the lungs, have established roles in tumor growth and metastasis; however, information about the role of macrophages in early carcinogenesis is limited. The purpose of this study was to evaluate the role of macrophages in modulation of tumor formation during different stages of urethane-induced lung carcinogenesis. To assess the role of macrophages in our lung tumor model, we developed a method of non-invasive long-term lung macrophage depletion by repetitive intratracheal injections of liposomal clodronate. Clodronate encapsulated liposomes are well known to cause selective apoptosis of macrophages. Depletion of macrophages during the entire experiment (4 Months) or during the late promotion and progression stages (Months 2-4), when macrophages primarily exhibited a M2 phenotype, significantly reduced tumor vasculogenesis and lung tumor multiplicity. Interestingly, depletion of alveolar macrophages during lung tumor initiation and early promotion stages (Week 1-2), when macrophages were polarized toward an M1 phenotype, caused similar attenuation of tumor vasculogenesis and lung carcinogenesis as observed after depletion of cells during the entire experiment or late promotion/progression stages. Moreover, early macrophage depletion, but not late depletion, significantly reduced formation of atypical adenomatous hyperplasia (AAH) lesions in the lungs. Our results demonstrate that macrophages are critical for promotion of lung carcinogenesis during early stages and suggest that the M1/M2 paradigm may not be an important concept for describing the impact of macrophages on tumor promotion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 451. doi:10.1158/1538-7445.AM2011-451