Toll-Like Receptor 3 Signaling in Breast Cancer Cells and the Recruitment of Leukocytes to the Tumor Microenvironment

Advanced stages of breast cancer are often associated with chronic inflammation in the tumor microenvironment that in turn attracts proangiogenic factors, resulting in neoangiogenesis. The upstream signaling that triggers this chronic inflammation is poorly understood. Toll-like receptors are a group of proteins involved in innate immunity and it was hypothesized that the over-stimulation of downstream TLR3 signaling could lead to the production of chemokines that cause leukocyte infiltration into the tumor microenvironment. In vitro stimulation of TLR3 using poly(I:C) and poly(A:U) yielded supportive results, showing an increase in the expression of RANTES, IL-6 and MIP-2 in both mouse mammary tumor cell line 4T1 and human breast cancer cell line MCF7. Further, treated 4T1 cell samples caused a greater percentage of migration of mouse dendritic cells and macrophages as compared to untreated samples in vitro. Lastly, TLR3 expression was knocked down by using siRNA. In the future, TLR3 knock down studies in vivo will help understand the effectiveness of targeting TLR3 in drug development.