惡性腫瘤細(xì)胞從原發(fā)部位，經(jīng)淋巴道,， 惡性腫瘤細(xì)胞從原發(fā)部位,，經(jīng)淋巴道， 血管或體腔等途徑,，到達(dá)其他部位繼續(xù)生長,，稱腫瘤轉(zhuǎn)移。
抑制血管生成一直是抗腫瘤轉(zhuǎn)移的一大有效途徑,。淋巴血管是腫瘤轉(zhuǎn)移的途徑之一,，在動(dòng)物模型中抑制腫瘤誘導(dǎo)的新生淋巴管可以有效抑制腫瘤轉(zhuǎn)移。
近日,，發(fā)育生物學(xué)家研究確定了轉(zhuǎn)錄因子SOX18在小鼠胚胎淋巴管生成中的關(guān)鍵開關(guān)作用,。該研究表明SOX18也是腫瘤誘導(dǎo)淋巴管生成的關(guān)鍵，抑制SOX18足以阻礙腫瘤轉(zhuǎn)移,。小鼠移植瘤的免疫熒光分析表明,，SOX18是腫瘤誘導(dǎo)淋巴管新生的關(guān)鍵因子。SOX18-缺陷小鼠體內(nèi)植入表達(dá)螢火蟲熒光素酶的B16-F10黑色素瘤細(xì)胞,，活體生物發(fā)光成像研究發(fā)現(xiàn)該細(xì)胞產(chǎn)生的腫瘤轉(zhuǎn)移至淋巴結(jié)的機(jī)率降低,。轉(zhuǎn)移率的降低與腫瘤淋巴管密度和直徑的減少呈正相關(guān)性。
總的來說,，研究結(jié)果表明SOX18是介導(dǎo)腫瘤淋巴管生成和轉(zhuǎn)移的關(guān)鍵因子,，有可能作為一個(gè)潛在的治療腫瘤轉(zhuǎn)移的靶標(biāo)。（生物谷：Bioon.com）
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.
