Abstract 5220: Inflamed and wound recovered tumor microenvironment contributions to lymphatic-mediated metastasis

Despite the clinical importance of lymph node status in cancer staging, treatment decisions, and patient outcomes, little is known about the earliest events of lymphatic-mediated metastasis of tumor cells. Lymphatic vessels remodel dramatically in response to changes in the inflammatory status of a tissue. Inflammation induces lymphangiogenesis and the resolution of inflammation stimulates lymphatic vessel regression. This study addresses one of the fundamental questions in metastasis biology and places it in the context of a specific microenvironmental state: how does a tumor cell gain entrance to a lymphatic vessel to migrate to a regional lymph node and what is the contribution of inflammation to this process? We sought to better understand lymphatic-mediated metastasis of tumor cells during inflammatory lymphangiogenesis or the resolution of inflammation. We hypothesized that manipulating the inflammatory status of the tumor microenvironment would alter tumor cell and lymphatic endothelium biology to influence lymphatic-mediated metastasis. We have previously established a corneal model of sutured-induced inflammatory lymphangiogenesis and a complimentary experimental arm of inflammation resolution. We transitioned this platform into real-time live imaging studies by using this corneal model in our novel transgenic mouse model background that inducibly expresses fluorescent tdTomato protein in the lymphatic endothelium (LyveCreERT2tdT). CFSE-labeled syngeneic tumor cells were introduced systemically via tail vein injection or locally into a corneal micropocket. Two-color intravital fluorescent stereomicroscopy allowed us to simultaneously track the fate of CFSE+ tumor cells at single-cell resolution and the morphologic changes in the tdTomato+ corneal lymphatic vessels during inflammatory lymphangiogenesis and lymphatic vessel regression. One major finding was the low frequency of lymphatic-mediated metastasis during both inflammation and resolution. Ongoing work continues to explore the contributions of specific cytokines to tumor-lymphatic endothelium interactions and the unique properties of a wound-recovered tumor microenvironment. Citation Format: Darci Marie Fink, Alicia L. Connor, Philip M. Kelley, Richard M. Tempero, Michael A. Hollingsworth. Inflamed and wound recovered tumor microenvironment contributions to lymphatic-mediated metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5220. doi:10.1158/1538-7445.AM2015-5220