Yahui Li1, Qing Cheng1, Zhaohui Xiong1, Chorlada Paiboonrungruang1, Timothy Adekoya1, Yong Li1,2, Xiaoxin Chen3,4. 1. Cancer Research Program, Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC, 27707, USA. 2. Department of Thoracic Surgery, National Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli Road, Beijing, 100021, China. 3. Cancer Research Program, Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC, 27707, USA. lchen@nccu.edu. 4. Center for Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. lchen@nccu.edu.
Abstract
BACKGROUND: Lymphatic metastasis is commonly seen in patients with esophageal squamous cell carcinoma (ESCC). Both lymphatic metastasis and the number of involved nodes are prognostic for post-operative survival. To better understand lymphatic metastasis of ESCC, there is a need to develop proper animal models. AIMS: This study is aimed to characterize the morphology and function of the lymphatic drainage system in the mouse esophagus. METHODS: Immunostaining and fluorescence imaging were used to visualize the lymphatic drainage system in the mouse esophagus. Tracers and cancer cells were orthotopically inoculated into the submucosa of the mouse esophagus to mimic lymphatic metastasis of T1 ESCC. RESULTS: Using immunostaining of a lymphatic vessel marker (LYVE1), we found that lymphatic vessels were located in the submucosa and muscularis propria of the mouse esophagus, similar to the human esophagus. In the esophagus of ProxTom mice expressing tdTomato in the lymphatic vessels, we discovered a microscopic meshwork of lymphatic vessels. Functionally, orthotopically inoculated tracers (Indian ink and FITC-dextran) were drained from the submucosa into peri-esophageal lymph nodes via lymphatic vessels. Orthotopically inoculated mouse cancer cells (LLC-eGFP, MOC2) metastasized from the submucosa to lymphatic vessels, peri-esophageal lymph nodes, and distant organs (liver and lung) in immunocompetent mice. Similarly, in immunodeficient mice, orthotopically inoculated human ESCC cells (KYSE450-eGFP-Luc) metastasized via the same route. CONCLUSION: We have characterized the morphology and function of the lymphatic drainage system of the mouse esophagus. These observations lay a foundation for mechanistic and therapeutic studies on lymphatic metastasis of T1 ESCC.
BACKGROUND: Lymphatic metastasis is commonly seen in patients with esophageal squamous cell carcinoma (ESCC). Both lymphatic metastasis and the number of involved nodes are prognostic for post-operative survival. To better understand lymphatic metastasis of ESCC, there is a need to develop proper animal models. AIMS: This study is aimed to characterize the morphology and function of the lymphatic drainage system in the mouse esophagus. METHODS: Immunostaining and fluorescence imaging were used to visualize the lymphatic drainage system in the mouse esophagus. Tracers and cancer cells were orthotopically inoculated into the submucosa of the mouse esophagus to mimic lymphatic metastasis of T1 ESCC. RESULTS: Using immunostaining of a lymphatic vessel marker (LYVE1), we found that lymphatic vessels were located in the submucosa and muscularis propria of the mouse esophagus, similar to the human esophagus. In the esophagus of ProxTom mice expressing tdTomato in the lymphatic vessels, we discovered a microscopic meshwork of lymphatic vessels. Functionally, orthotopically inoculated tracers (Indian ink and FITC-dextran) were drained from the submucosa into peri-esophageal lymph nodes via lymphatic vessels. Orthotopically inoculated mouse cancer cells (LLC-eGFP, MOC2) metastasized from the submucosa to lymphatic vessels, peri-esophageal lymph nodes, and distant organs (liver and lung) in immunocompetent mice. Similarly, in immunodeficient mice, orthotopically inoculated human ESCC cells (KYSE450-eGFP-Luc) metastasized via the same route. CONCLUSION: We have characterized the morphology and function of the lymphatic drainage system of the mouse esophagus. These observations lay a foundation for mechanistic and therapeutic studies on lymphatic metastasis of T1 ESCC.