Genetic ablation of SOX18 function suppresses tumor lymphangiogenesis and metastasis of melanoma in mice.

Duong, Tam; Proulx, Steven T; Luciani, Paola; Leroux, Jean-Christophe; Detmar, Michael; Koopman, Peter; Francois, Mathias (2012). Genetic ablation of SOX18 function suppresses tumor lymphangiogenesis and metastasis of melanoma in mice. Cancer research, 72(12), pp. 3105-3114. American Association for Cancer Research AACR 10.1158/0008-5472.CAN-11-4026

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Proulx, Steven Thomas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0008-5472

Publisher:

American Association for Cancer Research AACR

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

26 Oct 2020 12:05

Last Modified:

26 Oct 2020 12:22

Publisher DOI:

10.1158/0008-5472.CAN-11-4026

PubMed ID:

22523034

BORIS DOI:

10.7892/boris.147319

URI:

https://boris.unibe.ch/id/eprint/147319

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