SO05 THE NATURE OF NEARBY LYMPHATICS DICTATES WHETHER A VASCULAR ENDOTHELIAL GROWTH FACTOR‐D (VEGF‐D) INDUCES TUMOR LYMPHATICS AND METASTASIS

Purpose Tumors secreting VEGF‐D or VEGF‐C proteins exhibit increased lymphatic vessel density and lymph node spread (1), however tumor depth and anatomical location also influence metastasis in some tumors. It is unclear whether tumor lymphatics mirror one of the normal lymphatic subtypes or if they form an independent phenotype, and how this may vary in different anatomical locations. We aimed to study lymphatics induced in a VEGF‐D+ tumor model (1), xenografted in different locations, to better understand the vessels that facilitate tumor spread. Methods We analysed lymphatics formed in mouse skin wounds and tissue from VEGF‐D+ or VEGF‐D‐ tumors in the ear or flank, using immunohistochemical lymphatic marker LYVE‐1 and confocal imaging of fluorescent‐labelled antibodies. Results VEGF‐D+ tumors that were adherent to skin induced abnormal lymphatic structures that promoted lymph node metastasis (89%) and exhibited morphologically abnormal lymphatics; whereas size‐matched tumors that were adherent to the underlying body wall (similar VEGF‐D levels) metastasised minimally (19%, p < 0.001) and contained no morphologically abnormal lymphatics. Analysis of ear wounds and tumors suggested that lymphatics sprout mainly from the ‘pre‐collector’ lymphatic subtype within skin. Conclusion Lymphangiogenic growth factors are important but tumor location also plays a role in metastasis. A distinct tumor lymphatic subtype may alsooffer new diagnostic or therapeutic molecular targets.