Enhanced cancer metastasis in mice deficient in vasohibin-1 gene.
Enhanced cancer metastasis in mice deficient in vasohibin-1 gene.
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DOI：
10.1371/journal.pone.0073931
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sato Y
中科院分区：
文献类型：
--
作者：
Ito S;Miyashita H;Suzuki Y;Kobayashi M;Satomi S;Sato Y
Vasohibin-1（VASH 1）是一种由血管内皮细胞产生的内源性血管生成抑制剂。我们以前报道过VASH 1（−/−）小鼠的肿瘤生长和肿瘤血管生成增加。在这里，我们研究了VASH 1是否在癌症转移中发挥任何作用。当将刘易斯肺癌（LLC）细胞接种在脚垫中以观察自发转移时，在VASH 1（-/-）小鼠中，肺转移连同腹股沟淋巴结转移显著增加。组织学分析显示，VASH 1（−/−）小鼠的足垫肿瘤血管更不成熟，壁细胞更少。然而，当LLC细胞被注射到尾静脉中时，肺转移的程度在野生型小鼠和VASH 1（-/-）小鼠之间没有变化。当培养的内皮细胞中的VASH 1被siRNA敲低时，我们观察到紧密连接的组分ZO-1的含量减少，该减少导致癌细胞穿过内皮细胞单层的迁移增加。这些结果表明，内源性VASH 1收紧内皮屏障，使肿瘤血管对癌症转移具有抵抗力。
Vasohibin-1 (VASH1) is isolated as an endogenous angiogenesis inhibitor produced by the vascular endothelium. We previously reported that tumor growth and tumor angiogenesis were augmented in VASH1 (−/−) mice. Here we examined whether VASH1 plays any role in cancer metastasis. When Lewis lung carcinoma (LLC) cells were inoculated in the footpad to observe spontaneous metastasis, a significant increase in lung metastasis together with inguinal lymph node metastasis was evident in the VASH1 (−/−) mice. Histological analyses revealed that vessels of the footpad tumor in VASH1 (−/−) mice were more immature, having fewer mural cells. However, when LLC cells were injected into a tail vein, the extent of lung metastasis was unchanged between wild-type mice and VASH1 (−/−) mice. When VASH1 in endothelial cells in culture was knocked-down by siRNA, we observed a decrease in the content of ZO-1, a component of tight junctions, which decrease resulted in increased transmigration of cancer cells across the endothelial cell monolayer. These results indicate that endogenous VASH1 tightens the endothelial barrier and makes tumor vessels resistant to cancer metastasis.
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