Cold shock domain protein A (CSDA) overexpression inhibits tumor growth and lymph node metastasis in a mouse model of squamous cell carcinoma
Cold shock domain protein A (CSDA) overexpression inhibits tumor growth and lymph node metastasis in a mouse model of squamous cell carcinoma
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冷休克结构域蛋白 A (CSDA) 过表达抑制鳞状细胞癌小鼠模型中的肿瘤生长和淋巴结转移
DOI：
10.1007/s10585-010-9343-y
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发表时间：
2010
影响因子：
4
通讯作者：
Kaneda Y
中科院分区：
文献类型：
--
作者：
Matsumoto G;Yajima N;Saito Y;Nakagami H;Omi Y;Lee U;Kaneda Y
癌细胞通过进入淋巴系统转移。区域淋巴结转移是口腔鳞状细胞癌转移的第一步，与疾病的预后密切相关。冷休克结构域蛋白A（CSDA）是一种DNA结合蛋白，通过与缺氧反应元件（HRE）和血清反应元件（SRE）直接结合来抑制血管生成和淋巴管生成。在我们的研究中，我们使用细胞系NR-S1 M，一种具有高淋巴结转移率的小鼠SCC模型。我们将编码全长小鼠CSDA的表达质粒转染到这些细胞中。重要的是，我们发现CSDA的过表达显著抑制NR-S1 M细胞中VEGF-A和VEGF-C的产生。CSDA在NR-S1 M细胞中的过表达抑制肿瘤生长，抑制区域淋巴结转移，并降低体内原发肿瘤中的血管和淋巴管密度。我们的研究结果支持这一假设，即VEGF-A和VEGF-C是NR-S1 M细胞中血管生成和淋巴管生成的重要调节因子。因此，它们是CSDA过表达基因治疗抑制SCC肿瘤生长和淋巴结转移的有希望的靶点。
Cancer cells metastasize by entering the lymphatic system. Regional lymph-node dissemination is the first detectable step in the metastasis of oral squamous cell carcinoma (SCC) and is highly correlated to the prognosis of the disease. Cold shock domain protein A (CSDA) is a DNA-binding protein that represses angiogenesis and lymphangiogenesis by directly binding to hypoxia response element (HRE) and serum response element (SRE). In our study we used the cell line NR-S1M, a mouse SCC model with a high rate of lymph-node metastasis. Into these cells we transfected the expression-plasmid coding for full-length mouse CSDA. Of importance, we showed that overexpression of CSDA significantly inhibits the production of VEGF-A and VEGF-C in NR-S1M cells. The overexpression of CSDA in NR-S1M cells inhibited tumor growth, inhibited regional lymph-node metastasis, and reduced the density of blood vessels and lymphatic vessels in the primary tumors in vivo. Our results support the hypothesis that VEGF-A and VEGF-C are crucial regulators of angiogenesis and lymphangiogenesis in NR-S1M cells. Therefore, they are promising targets for CSDA overexpression gene therapy to inhibit tumor growth and lymph-node metastasis in SCC.