Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Genetic ablation of SOX18 function suppresses tumor lymphangiogenesis and metastasis of melanoma in miceĀ  (#157)

Tam Duong 1 , Steven Proulx 2 , Paola Luciani 2 , Jean-Christophe Leroux 2 , Michael Detmar 2 , Peter Koopman 1 , Mathias Francois 1
  1. University of Queensland, Brisbane, QLD, Australia
  2. 2. Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology ETH, Zurich, Switzerland

The lymphatic vasculature provides a major route for tumor metastasis and inhibiting neo-lymphangiogenesis induced by tumors can reduce metastasis in animal models. Developmental biology studies have identified the transcription factor SOX18 as a critical switch for lymphangiogenesis in the mouse embryo. Here, we show that SOX18 is also critical for tumor-induced lymphangiogenesis and we demonstrate that suppressing SOX18 function is sufficient to impede tumor metastasis. Immunofluorescence analysis of murine tumor xenografts showed that SOX18 is re-expressed during tumor-induced neo-lymphangiogenesis. Tumors generated by implantation of firefly luciferase-expressing B16-F10 melanoma cells exhibited a reduced rate of metastasis to the regional draining lymph node in Sox18-deficient mice, as assessed by live bioluminescence imaging. Lower metastatic rates correlated with reduced tumoral lymphatic vessel density and diameter, and with impaired drainage of peri-tumoral injected liposomes specific for lymph vessels from the sentinel lymph nodes. Overall, our findings suggested that SOX18 induction is a key step in mediating tumor lymphangiogenesis and metastasis, and they identify SOX18 as a potential therapeutic target for metastatic blockade.