Abstract 2335: Breast cancer cell-derived DNA activates STING pathway in macrophages

Abstract

Abstract Cell-free DNA (cfDNA) has been studied to be a diagnostic and prognosic marker. In breast cancer, however, there have been few studies on the biological role of cfDNA in the tumor microenvironment. Thus, investigating a role of cfDNA released from cancer cells to the tumor microenvironment is important in order to understand cancer biology. In this study, we showed that free DNA was a mediator that elicited inflammation and activated stimulator of interferon genes (STING) signaling, an essential pathway in cytosolic DNA-associated innate immune reponses in breast cancer. First, we found that mRNA levels of pro-inflammatory cytokines were increased in THP-1 macrophage cells co-cultured with MDA-MB-231 breast cancer cells. Second, the amount of free double strand DNA derived from MDA-MB-231 cells culture media was much more than THP-1 cells. Third, there was little induction of STING pathway in response to exogenous DNA in MDA-MB-231 cells, suggesting that cancer cells may not be sensitive to exogenous DNA for activating STING pathway. In contrast, STING pathway was activated in response to exogenous DNA in THP-1 cells. Taken together, cancer cell-derived DNA could be a factor to induce inflammation through activating STING pathway in tumor-associated macrophages. Citation Format: GaYoung LIM, Na-Lee Ka, Mi-Ock Lee. Breast cancer cell-derived DNA activates STING pathway in macrophages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2335.