SAT-136 Hypoxia Effect on Cytokine Production by Breast Cancer Cells

Abstract

Inflammation is a critical component of tumor initiation and progression. Chronic inflammation triggers molecular events that can promote carcinogenesis, tumor vascularization and metastasis. As inflammatory mediators, cytokines play an important role in the interplay between the tumor cells and tumor microenvironment. Cytokines released by the tumor-associated macrophages modulate cancer cell survival, stemness, invasiveness, and tumor vascularization. Breast cancer cells, however, also produce a variety of cytokines, whose role in cancer development is poorly understood. The aim of our study was to characterize the basal cytokine secretory activity in commonly used human breast cancer cell lines (MDA-MB-231, MCF-7, BT-474, and T-47D). Using MILLIPLEX assay, we measured the expression of 41 cytokines, including interleukins, monokines, interferons and growth factors. We also compared cytokine expression profile of breast cancer cells with those of non-tumorigenic human breast epithelial MCF-10A cells. Further, we investigated whether hypoxia modulates cytokine secretion of breast cancer cells. Using cobalt(II) chloride (CoCl2) to mimic hypoxia, we compared the effect of various treatment doses and intervals on cytokine production in the breast cancer cells. Results demonstrated that CoCl2 affects the release of multiple cytokines in a dose- and concentration-dependent manner, thus highlighting the role of cancer cell-derived cytokines on breast tumor progression. Understanding the molecular actions of cytokines in the tumor microenvironment is important for understanding the mechanism of cancer initiation and progression.