Cancer Res：抑制SOX18降低小鼠黑色素瘤转移

恶性肿瘤细胞从原发部位，经淋巴道， 恶性肿瘤细胞从原发部位，经淋巴道， 血管或体腔等途径，到达其他部位继续生长，称肿瘤转移。

抑制血管生成一直是抗肿瘤转移的一大有效途径。淋巴血管是肿瘤转移的途径之一，在动物模型中抑制肿瘤诱导的新生淋巴管可以有效抑制肿瘤转移。

近日，发育生物学家研究确定了转录因子SOX18在小鼠胚胎淋巴管生成中的关键开关作用。该研究表明SOX18也是肿瘤诱导淋巴管生成的关键，抑制SOX18足以阻碍肿瘤转移。小鼠移植瘤的免疫荧光分析表明，SOX18是肿瘤诱导淋巴管新生的关键因子。SOX18-缺陷小鼠体内植入表达萤火虫荧光素酶的B16-F10黑色素瘤细胞，活体​​生物发光成像研究发现该细胞产生的肿瘤转移至淋巴结的机率降低。转移率的降低与肿瘤淋巴管密度和直径的减少呈正相关性。

总的来说，研究结果表明SOX18是介导肿瘤淋巴管生成和转移的关键因子，有可能作为一个潜在的治疗肿瘤转移的靶标。

doi:10.1158/0008-5472.CAN-11-4026
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Genetic Ablation of SOX18 Function Suppresses Tumor Lymphangiogenesis and Metastasis of Melanoma in Mice

Tam Duong, Steven T. Proulx, Paola Luciani, Jean-Christophe Leroux, Michael Detmar, Peter Koopman, and Mathias Francois

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.