Abstract 115: Crosstalk between breast cancer cells and macrophages in tumor microenvironment induces inflammasome activation

Abstract

Abstract The inflammasome is a multiprotein complex that is composed of NOD-like receptor, ASC and caspase-1. During the activation of the inflammasome, pro-interleukin (IL)-1β is cleaved by active caspase-1 to produce mature IL-1β. Although the inflammasome plays a controversial role in many types of tumor, emerging evidence indicates that the inflammasome functions as a negative regulator of breast cancer progression. Notably, high levels of IL-1β in breast cancer tissues are associated with a more virulent tumor phenotype and poor prognosis. However, it remains unresolved how IL-1β is accumulated in breast tumor microenvironment. In the present study, we have found that various human breast cancer cells (MDA-MB-231, MDA-MB-468, SKBr3, MCF-7 and T47D) retain cleaved-IL-1β whereas secretion of IL-1β into the culture medium was not observed. However, IL-1β was detected in the medium when human breast cancer cells were co-cultured with human monocytic (THP-1) cells. Among the various human breast cancer cells, triple-negative breast cancer cells (MDA-MB-231 and MDA-MB-468) effectively stimulated secretion of IL-1β. When co-cultured with MDA-MB-231 cells, THP-1 cells exhibited the elevated levels of pro- and cleaved-IL-1β. Consistent with this result, there was a marked increase in the secretion of IL-1β from THP-1 cells treated with the conditioned media of triple-negative breast cancer cells. Both triple-negative MDA-MB-231 and MDA-MB-468 breast cancer cells induced ASC oligomerization, which is a hallmark of inflammasome activation. Thus, it is likely that soluble factors from breast cancer cells promote IL-1β secretion from macrophages through activation of inflammasomes. In conclusion, breast cancer cells drive inflammasome activation in macrophages, thereby stimulating the accumulation of IL-1β in the tumor microenvironment. The secreted-IL-1β, in turn, promotes breast cancer progression. Citation Format: Jeong-Hoon Jang, Do-Hee Kim, Sin-Aye Park, Su-Jung Kim, Young-Joon Surh. Crosstalk between breast cancer cells and macrophages in tumor microenvironment induces inflammasome activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 115.