Abstract 114: Basal-like breast cancer engages tumor-supportive macrophages via cytokines triggered by extracellular S100A4

Abstract

Abstract Recently the biological and therapeutic perspective on cancer has evolved from focusing on tumor cells only, to include the complex impact of the tumor microenvironment (TME). The TME appears to have a strong influence on both tumor progression and response to treatment. In breast cancer, and in particular the triple-negative subgroup, patient outcome together with the therapeutic response are strongly linked to the tumor's inflammatory profile: presence of tumor-infiltrating leukocytes and their regulatory cytokine. Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the TME, and expression of such cells has been strongly correlated with both poor outcome and development of resistance. In this study we explored the effect of the pro-metastatic, inflammation-associated, TME factor S100A4 on breast cancer cells (BCCs) of different subtypes, and their further interactions with inflammatory cells. We show that S100A4 activates BCCs, stimulating secretion of pro-inflammatory cytokines, which, in turn, promotes monocyte conversion into TAM-like cells. This was in particular prominent for cytokines secreted from basal-like BCCs. The TAM-like cells possess pro-tumorigenic activities, including increased resistance and ability to migrate. In conclusion, we demonstrate that S100A4 instigate an inflammatory microenvironment, involving a network of cytokines and TAMs, which is particularly pronounced in basal-like BC and could facilitate aggressive phenotypes of this subtype. Citation Format: Lina Prasmickaite, Ellen M. Tenstad, Eivind Valen Egeland, Solveig Pettersen, Shakila Jabeen, Silje Nord, Mads Haugland Haugen, Siri Juell, Tove Øyjord, Olav Engebråten, Gunhild Mari Mælandsmo. Basal-like breast cancer engages tumor-supportive macrophages via cytokines triggered by extracellular S100A4 [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 114.