The Role of CXCR3 in Breast Cancer Tumorigenesis caused by PyMT Cell Line

Abstract

Breast cancer is responsible for the highest number of cancer related deaths in women each year. Recent breast cancer patient studies have shown that tumor cell expression of CXCR3, a chemokine receptor, results in poor overall survival. Conversely, another study shows that expression of CXCR3 on activated CD8 T cells enable migration to cancer sites, thereby contributing to tumor rejection. The purpose of this research is to determine whether or not CXCR3 plays a role in the tumorigenesis in a PyMT breast cancer mouse model. We examined the role of CXCR3 in breast cancer in vivo by infecting female CXCR3-/- and wild type mice with a Polyoma Middle T antigen (PyMT) breast cancer cell line. The immune response to the induction of tumorigenesis was examined through tumor measurements and FACS analysis of mouse tumors, spleens and lymph nodes. Initial findings indicate a significantly enhanced tumor growth in knockout mice, with knockout mice displaying tumor volumes three orders of magnitude greater than wild type mice. Further, the spleens and lymph nodes of CXCR3-/- mice contained lower numbers of infiltrating CD8+ T cells and CD4+ T cells and showed elevated numbers of alternatively activated macrophages (M2). In conclusion, our results demonstrate that CXCR3 plays a role in the immune response to tumorigenesis in a PyMT breast cancer