Abstract 4942: Metastatic tumor migration in lymphatic vessels revealed by real-time intravital imaging

Distant tumor metastases and their confounding symptoms are often responsible for reduced patient quality-of-life and decreased overall survival. The main route of metastasis for many solid tumors is the lymphatic vasculature. The mechanisms of metastatic spread of tumor cells through the lymphatic vessels remain poorly understood. We have developed a novel transgenic mouse model and customized real-time intravital microscopy platforms to study the migration of tumor cells into lymphatic vessels in live animals over the course of several days. TdTomato fluorescent protein was expressed in lymphatic endothelial cells using an inductive CRE recombinase approach. This transgenic system coupled with the use of fluorescent stereomicroscopy techniques allowed us to visualize the cutaneous lymphatic vessel network with remarkable anatomic detail in living mice. We tracked the fate of CFSE-labeled B16 tumor cells administered cutaneously using two-color intravital fluorescence microscopy. This strategy allowed us to simultaneously visualize the lymphatic vessel network (red) and the B16 tumor cells (green) at single-cell resolution. We clearly visualized and documented several key behaviors of metastasizing tumor cells including single-cell intravasation, movement of tumor cells within vessels, clearing from vessels, and the accumulation of tumor cells in regional lymph nodes. These events occurred at a low frequency over the course of days in conditions of tissue homeostasis. Current studies are designed to define the anatomic site of tumor intravasation into lymphatic vessels and investigate how the inflamed tumor microenvironment affects tumor migration into the lymphatic vasculature. Citation Format: Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Richard M. Tempero, Michael A. Hollingsworth. Metastatic tumor migration in lymphatic vessels revealed by real-time intravital imaging. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4942. doi:10.1158/1538-7445.AM2014-4942