Sentinel Lymph Node Metastases In Breast Cancer: A Contributor To Distant Metastases?

Breast cancer metastasis remains a major cause of mortality in patients. Although significant progress has been made in understanding the mechanisms of this complex process, the findings have yet to be translated into improved survival rates in patients with metastatic disease. The presence of lymph node metastasis in most breast cancer patients is associated with tumor aggressiveness, poorer prognosis and often results in the need for systemic therapy. However, whether tumor cells in the lymph node exit and contribute to distant metastases remains controversial. To track the fate of tumor cells that metastasized to the lymph node, we engineered breast tumor cell lines to express Dendra2, a photo-convertible protein that fluoresces green in the native state and on light activation converts to red fluorescence. Using a novel chronic lymph node window that allows time-lapse imaging over a period of 10 days, we were able to track the movement of cancer cells in the dynamic microenvironment using high- resolution multi-photon microscopy. Our studies show that tumor cells entering the lymph node through the afferent lymphatic vessel proliferate in the sub-capsular sinus and later begin to invade the lymph node parenchyma. Importantly, by photo-conversion of tumor cells in the lymph node, we are able to track the tumor cells that escaped the lymph node and entered the blood circulation. The circulating tumor cells that transited through the lymph node were viable and proliferated in vitro. Our data indicate that metastatic breast cancer cells can exit the node and potentially colonize distant organs. Citation Format: Pereira ER, Kedrin D, Jones D, Beech E, Taghian A, Padera TP. Sentinel lymph node metastases in breast cancer: A contributor to distant metastases?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-22.