An Optimized Coculture System Utilized to Determine Differentiation and Polarization States of THP- (2011)

Undergraduates: Yinmeng Yang, Delisha Stewart PhD (postdoc)

Faculty Advisor: Melissa Troester
Department: Biology

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Basal-like breast cancer (BBC) is a comparatively aggressive subtype of breast cancer (BCa) that has no current targeted treatment. Recent data suggests that the growth of basal-like breast cancer may be promoted by macrophages and inflammation. The objective of this study was to design a stable system to monitor how basal-like breast cancer affects monocyte-to-macrophage differentiation and polarization in the microenvironment. A coculture model system was used, where breast cancer cells were grown with a macrophage model cell line, to elucidate biologically significant signals. Once optimized, this system enabled us to evaluate the impact of breast cancer-derived secreted factors on the differentiation and polarization states of macrophages. We hypothesized those basal-like breast cancer epithelial cells would favor polarization to M2 macrophages, the primary class found in tumor microenvironments. Polarization of THP-1 cells when cocultured with basal-like breast cancer cells was compared to polarization induced by luminal breast cancer cells. Positive controls included treatment of THP-1 cells with phorbol myristate acetate (PMA) and M1- or M2-polarizing cytokines. The project is providing data to elucidate the relationships between basal-like breast cancer and its microenvironment.