Abstract 3022: Lymph node metastasis in solid tumors: A marker or driver of disease progression

Background: The presence of lymph node metastasis in patients with solid tumors is associated with tumor aggressiveness, poorer prognosis and the recommendation for systemic therapy. However, whether tumor cells exit the lymph node and contribute to distant metastases remains controversial. Methods: In this study, we used syngeneic murine cell lines representing breast and melanoma cancer that spontaneously metastasize to the lymph node. We engineered these cells to express Dendra2, a photoconvertable protein. Dendra2 is a green-fluorescent protein that can be converted to emit red light by exposure to 405nm light. Once tumor cells spontaneously metastasized to the lymph node from the primary site, a 405nm laser diode was used on 5 consecutive days to convert Dendra2-cancer cells from green to red fluorescence, restricting the light exposure only to the metastatic lymph node. This technology allowed us to specifically trace the fate of cancer cells in the lymph node and beyond to other organs. Results: We show that spontaneous lymph node metastasis from breast cancer and melanoma mouse models can leave the lymph node and enter the blood circulation. We identified micrometastatic disease in the lung that originated from the lymph node in both models. We hypothesized that cancer cells escape the lymph node by directly invading lymph node blood vessels, as opposed to draining through the efferent lymphatic vessel. Immunohistochemical analysis of metastatic lymph nodes revealed isolated cancer cells in close association with CD31+ blood vessels, within high endothelial venules (HEVs) and breaching the vascular basement membrane. Quantitative analysis showed that 23±2% of isolated cancer cells were within 5μm of a blood vessel, compared to only 11±1% using a predictive model of randomly distributed cells in the lymph node (p Citation Format: Ethel R. Pereira, Dmitriy Kedrin, Giorgio Seano, Olivia Gautier, Eelco F. Meijer, Dennis Jones, Shan-Min Chin, Shuji Kitahara, Echoe M. Bouta, Jonathan Chang, Elizabeth Beech, Han-Sin Jeong, Michael C. Carroll, Alphonse G. Taghian, Timothy P. Padera. Lymph node metastasis in solid tumors: A marker or driver of disease progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3022.