Abstract 3351: NF-κB signaling between stromal macrophages and breast cancer cells

Abstract

Abstract It has become increasingly clear that the tumor microenvironment directly interacts with tumor cells to promote tumor growth and progression. Tumor associated macrophages (TAMs) have emerged as key components of the tumor microenvironment, and their presence in breast cancer is associated with poor prognosis. There is evidence that nuclear factor -kappaB (NF-κB) is an important signaling pathway between cancer cells and the stromal compartment. Disruption of NF-κB communication between TAMs and breast tumors may weaken the pro-tumorigenic influences of TAMs, and therefore make the tumor more susceptible to standard treatments. Our work reveals that when breast cancer cells and bone marrow derived macrophages (BMDMs) are co-cultured in transwell plates, activated canonical NF-κB and STAT3 levels dramatically increase in both cell types. This signaling interaction was confirmed by co-culturing human blood derived macrophages with breast cancer cells. BMDMs co-cultured with breast cancer cells acquire a mixed M1/M2 activation phenotype, and also have skewed inflammatory cytokine production. In basal-like mouse tumors, active NF-κB levels are much higher in the CD11b+ (TAM) fraction compared to the CD11b- fraction. Even more so than BMDMs, TAMs isolated from mouse basal-like tumors have high NF-κB activity, and can promote elevated NF-κB and STAT3 activation and cytokine production in breast cancer cells when co-cultured in transwell plates. BMDMs genetically lacking p65 have altered inflammatory cytokine production when compared to wild type BMDMs, which remains skewed when the cells are co-cultured with breast cancer cells. Because the NF-κB pathway can be targeted therapeutically, understanding how NF-κB activation influences breast tumor-TAM communication is important for developing new treatment options for aggressive cancers. Citation Format: Jennifer W. Bradford. NF-κB signaling between stromal macrophages and breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3351. doi:10.1158/1538-7445.AM2015-3351