Suppression of lymph node and lung metastases of endometrial cancer by muscle-mediated expression of soluble VEGF receptor-3
Suppression of lymph node and lung metastases of endometrial cancer by muscle-mediated expression of soluble VEGF receptor-3
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通过肌肉介导的可溶性 VEGF 受体 3 表达抑制子宫内膜癌的淋巴结和肺转移
DOI：
10.1111/cas.12184
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发表时间：
2013
期刊：
影响因子：
5.7
通讯作者：
Ozawa K
中科院分区：
文献类型：
--
作者：
Takahashi K;Mizukami H;Saga Y;Takei Y;Urabe M;Kume A;Machida S;Fujiwara H;Suzuki M;Ozawa K
淋巴结转移是子宫内膜癌最重要的预后因素。然而，针对淋巴结转移的有效治疗尚未建立。在这项研究中，我们通过可溶性血管内皮生长因子受体-3（sVEGFR-3）表达抑制血管内皮生长因子（VEGF）-C的作用，探索针对子宫内膜癌淋巴结转移的基因治疗的功效。为此，我们首先通过将sVEGFR-3 cDNA导入子宫内膜癌细胞系HEC 1A进行了模型实验，并建立了sVEGFR-3高表达的HEC 1A/sVEGFR-3细胞系。HEC 1A/sVEGFR-3细胞的条件培养液在体外可抑制淋巴管内皮细胞的生长，并可抑制HEC 1A细胞中sVEGFR-3的表达，但对皮下接种的肿瘤生长无抑制作用。为了验证治疗效果，将编码sVEGFR-3的腺相关病毒载体注射到具有淋巴结转移的小鼠的骨骼肌中。使用腺相关病毒载体，肌肉介导的sVEGFR-3表达完全抑制了HEC 1A细胞的淋巴结和肺转移。这些结果表明，通过使用肌肉介导的sVEGFR-3表达对子宫内膜癌的淋巴结和肺转移进行基因治疗的可能性。
Lymph node metastasis is the most important prognostic factor of endometrial cancer. However, effective therapy has not been established against lymph node metastasis. In this study, we explored the efficacy of gene therapy targeting lymph node metastasis of endometrial cancer by suppressing the action of vascular endothelial growth factor (VEGF)‐C through soluble VEGF receptor‐3 (sVEGFR‐3) expression. For this purpose, we first conducted a model experiment by introducing sVEGFR‐3 cDNA into an endometrial cancer cell line HEC1A and established HEC1A/sVEGFR‐3 cell line with high sVEGFR‐3 expression. The conditioned medium of HEC1A/sVEGFR‐3 cells inhibited lymphatic endothelial cell growthin vitro, and sVEGFR‐3 expression in HEC1A cells suppressedin vivolymph node and lung metastases without inhibiting the growth of a subcutaneously inoculated tumor. To validate the therapeutic efficacy, adeno‐associated virus vectors encoding sVEGFR‐3 were injected into the skeletal muscle of mice with lymph node metastasis. Lymph node and lung metastases of HEC1A cells were completely suppressed by the muscle‐mediated expression of sVEGFR‐3 using adeno‐associated virus vectors. These results suggest the possibility of gene therapy against lymph node and lung metastases of endometrial cancer by using muscle‐mediated expression of sVEGFR‐3.