Abstract P1-01-18: Disrupting interactions between human breast cancer cells, adipocytes, and macrophages

Abstract

Abstract An increasing number of studies have found that other cells in the tumor microenvironment can influence tumor cells. Adipocytes, which were once thought to function only in energy storage, are now considered an active endocrine organ that secretes pro-inflammatory cytokines and proteases. In human breast cancer patients, invading tumor cells are surrounded by mature adipocytes. The breast cancer cells cause the adipocytes to undergo phenotypic changes and overexpress pro-inflammatory cytokines and matrix metalloproteinases (MMPs), such as MMP-3 and MMP-11. The presence of the changed adipocytes then increases the invasion capacity of breast cancer cells. Obesity is an important breast cancer risk factor. It causes changes to adipocytes and the surrounding microenvironment by invasion of macrophage cells. The effects of obesity-induced macrophage invasion have not been well characterized in the sector of breast cancer-adipocyte crosstalk. A novel 3D co-culture system was used to investigate how macrophage-induced inflammation can worsen this crosstalk, and what changes are involved in cytokine expression, adipocyte de-differentiation, breast cancer aggressiveness, and extracellular matrix (ECM) composition. When macrophage conditioned media was added to adipocytes and breast cancer cells in co-culture, the breast cancer cells showed increased cell proliferation and migration abilities. Experimental co-culture (adipocytes, breast cancer cells, macrophage conditioned media) showed almost twice the number of cells than the control co-culture (adipocytes, breast cancer cells, non-conditioned media). Interestingly, breast cancer cells alone in macrophage conditioned media did not show an increase in proliferation. This shows that macrophages may not affect breast cancer proliferation directly, as all three cell types are needed for increased proliferation of breast cancer cells. Introducing macrophages into this crosstalk also resulted in increased migration abilities. After 24 hours, breast cancer cells grown in experimental co-culture migrated further to close a wound than breast cancer cells grown in control co-culture. These results show that macrophages can affect adipocyte-breast cancer cell crosstalk. This may help explain why obese breast cancer patients have worse prognosis than non-obese breast cancer patients. Further investigation into these effects may identify targets to improve prognosis and abate breast cancer aggressiveness in obese breast cancer patients. Citation Format: Vallega KA, Sang Q-XA. Disrupting interactions between human breast cancer cells, adipocytes, and macrophages [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-01-18.