Genetic ablation of SOX 18 function suppresses tumor lymphangiogenesis and metastasis of melanoma in mice

Duong, Tam, Proulx, Steven T., Luicani, Paola, Leroux, Jean-Christophe, Detmar, Michael, Koopman, Peter and Francois, Mathias (2012) Genetic ablation of SOX 18 function suppresses tumor lymphangiogenesis and metastasis of melanoma in mice. Cancer Research, 72 12: 3105-3114. doi:10.1158/0008-5472.CAN-11-4026


Author Duong, Tam
Proulx, Steven T.
Luicani, Paola
Leroux, Jean-Christophe
Detmar, Michael
Koopman, Peter
Francois, Mathias
Title Genetic ablation of SOX 18 function suppresses tumor lymphangiogenesis and metastasis of melanoma in mice
Journal name Cancer Research   Check publisher's open access policy
ISSN 1538-7445
0008-5472
Publication date 2012-06
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-11-4026
Volume 72
Issue 12
Start page 3105
End page 3114
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2013
Language eng
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 01 Aug 2012, 14:11:48 EST by Susan Allen on behalf of Institute for Molecular Bioscience