Abstract 2817: The contribution of bone marrow cells to carcinogenesis in the chronic inflammatory lung conditions.

Abstract

Abstract The role of inflammation in lung carcinogenesis is suggested by the independent association between chronic obstructive lung disease, a systemic inflammatory process, and lung cancer risk. To investigate that chronic inflammation in the lung potentiates tobacco smoke-induced lung carcinogenesis, we utilized two murine models of chronic lung inflammation: a model of sustained intranasal exposure to lipopolysaccharide (LPS) and a transgenic model of inducible interleukin-1β overexpression in the lung. In preliminary experiments, nicotine-derived nitrosamine (NNK) tobacco carcinogen induced tumor multiplicity is significantly increased in stress markers in the lung tumors with chronic inflammation. To determine the role of bone marrow-derived stem cells (BMDCs) in mediating the oxidative stress response in this model of chronic lung inflammation, we performed lineage tracing experiments. BMDCs are capable of self-renewal and recruited to the end organs where they differentiate into various terminal cells. In inflammation-associated gastric cancer, BMDCs contribute to the tumor microenvironment both by direct proliferation of epithelial cells and by differentiation into α-SMA positive cancer-associated fibroblasts. We hypothesize that BMDCs are recruited to inflammatory sites and contribute to the process of lung carcinogenesis through differentiation. We performed bone marrow transplantation from male GFP tagged donors to female chronic lung inflammation models. We investigated the localization and quantification of BMDCs contributions to subsequent lung tumors by immunohistochemistry of GFP and FISH for the Y chromosome. Additionally, we examined the differentiation of BMDCs in the tumor and associated microenvironment. This study has the potential to identify novel pathways of lung carcinogenesis in cigarette carcinogen-induced lung cancers arising in the setting of chronic inflammation. Citation Format: Sachiko Takikawa, Charles Powell. The contribution of bone marrow cells to carcinogenesis in the chronic inflammatory lung conditions. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2817. doi:10.1158/1538-7445.AM2013-2817