Carter, KiahRae J.
Orlowski, Ashley
Hodge, Lisa


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Breast cancer is the leading cause of cancer-related deaths. More research needs to be done to examine the role of the lymphatic system during metastasis and therapies directed at the lymphatic system. Our rat model was used because it closely mimics human breast cancer. These results will allow for the future studies of therapies targeting the lymphatic system and if they will prevent metastasis. Purpose (a): Breast cancer is the leading cause of cancer-related morbidity and mortality. New research suggests the lymphatic vessels play a key role during the metastasis of breast cancer and therapies directed at the lymph system may aid in the treatment of breast cancer. MTLn3 is a mammary adenocarcinoma that is commonly used to study the effects of tumor metastasis in Fischer 344 rats. MTLn3 closely mimics human breast cancer pathogenesis, making it ideal for the study of breast cancer disease; however, little is known about the role of the lymphatic and immune systems in this disease model. The purpose of this study was to identify the type of immune response generated during MTLn3 disease. Specifically, we proposed that natural killer cells (NK), T cells, B cells and macrophages (MO) would increase in response to disease. Methods (b): To test our hypothesis, rats were randomized into control group or were sub-cutaneously injected in the right mammary fat pad with 1x106 MTLn3 tumor cells/mL on day 0. At days 0, 7, 14, 21 and 25 post-injection, lungs, tumor-adjacent lymph nodes (ALN), tumor–opposite lymph nodes (OLN) and spleens were removed and the concentration of leukocytes was determined. Primary tumors were excised and measured to calculate tumor volume. Blood was analyzed for the complete blood count and serum was measured for cancer-specific biomarkers. Results (c): All animals gained weight until day 14 post-injection. However, rats injected with MTLn3 suffered weight loss between days 14-25 post-injection. Furthermore, primary tumor size significantly (p < 0.05) increased during this time, suggesting weight loss may be related to disease. CD4+ T cells, B cells and MO in the spleen at day 21 decreased by day 25. Tumor adjacent lymph nodes experienced an increase in all cell populations, T cells, B Cells, MO, dendritic cells and NK. There were no differences in cell populations between ALN and OLN, except MO were significantly (p < 0.05) increased in ALN at Day 25. There was no change in pulmonary leukocytes by day 25. Neutrophils, monocytes and lymphocytes in the blood were significantly (p < 0.05) increased between control and 25 days post-injection rats, suggesting there is an immune response against MTLn3 tumor cells. Conclusions (d): Collectively, our results suggest MTLn3 initiates an immune response mediated by T cells, B cells, macrophages and NK cells between days 14-25 of disease. Of interest, these cells increase in the ALN at day 25 post-injection, suggesting they migrate into the lymph nodes in response to disease. In future studies, we will determine if MTLn3 metastasizes to the sentinel lymph nodes and the lung and determine if therapies targeting the lymphatic system inhibit this process.