title: Genetic ablation of SOX18 function suppresses tumor lymphangiogenesis and metastasis of melanoma in mice.
abstract: The lymphatic vasculature provides a major route for tumor metastasis and inhibiting neolymphangiogenesis 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 show that suppressing SOX18 function is sufficient to impede tumor metastasis. Immunofluorescence analysis of murine tumor xenografts showed that SOX18 is reexpressed during tumor-induced neolymphangiogenesis. 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 peritumoral 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.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
authors.forename: Tam
authors.initials: T
authors.lastname: Duong
authors.forename: Steven T
authors.initials: ST
authors.lastname: Proulx
authors.forename: Paola
authors.initials: P
authors.lastname: Luciani
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Leroux
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
authors.forename: Peter
authors.initials: P
authors.lastname: Koopman
authors.forename: Mathias
authors.initials: M
authors.lastname: Francois
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology / Q000502:physiology; D008546:Melanoma, Experimental / Q000473:pathology* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D055760:SOXF Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
chemical_list: D055760:SOXF Transcription Factors; C490653:Sox18 protein, mouse