The Role of CXCL10 (IP 10) in Breast Cancer/ Stromal Macrophage Interactions

Abstract

Breast cancer is the second most deadly cancer with more than 260,000 people being diagnosed, and over 40,900 dying from it annually in the United States. This project focuses on triple negative breast cancer (TNBC), which is very aggressive due to the lack of hormone receptors. TNBC is characterized by an expansive stromal compartment that contains a large percentage of immune system macrophages, which correlates with poor patient prognosis. The Bradford lab has identified that the chemokine CXCL10 was found to be decreased at the mRNA and protein levels in TNBC cells when co-cultured with macrophages. The loss of CXCL10 might result in less destruction of tumors. To better understand the decrease in CXCL10, a cell invasion assay investigating invasion ability of the MDA-MB231 TNBC cell line was completed using macrophage conditioned media, with and without recombinant CXCL10, or a CXCL10 neutralizing antibody. We also investigated whether the NF-kappaB signaling pathway was involved by using primary bone marrow-derived macrophages from a NF-kappaB knockout mouse. The cell invasion assay showed that altering CXCL10 and NF-kappaB signaling in macrophages and/or the MDA-MB231 cells leads to differences in invasion ability.