Vasohibin-1 Expression in Endothelium of Tumor Blood Vessels Regulates Angiogenesis
Vasohibin-1 Expression in Endothelium of Tumor Blood Vessels Regulates Angiogenesis
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DOI：
10.2353/ajpath.2009.080788
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发表时间：
2009-07-01
影响因子：
6
通讯作者：
Sato, Yasufumi
中科院分区：
文献类型：
--
作者：
Hosaka, Tomoko;Kimura, Hiroshi;Sato, Yasufumi
在这项研究中，我们表征了血管内皮生长因子诱导型血管生成抑制剂 vasohibin-1 对肿瘤的重要性。在非小细胞肺癌的病理切片中，vasohibin-1存在于肿瘤间质血管内皮细胞中，但不存在于淋巴管中。在癌细胞中，vasohibin-1 的存在与缺氧诱导因子 1 α/血管内皮生长因子和成纤维细胞生长因子-2 的表达相关。然后，我们通过皮下接种 Lewis 肺癌细胞来检查 vasohibin-1 在小鼠体内的功能。与野生型小鼠的肿瘤相比，vasobibin-1(-/-) 小鼠的肿瘤含有更多的未成熟血管和更少的凋亡肿瘤细胞。在接种Lewis肺癌细胞的野生型小鼠中，尾静脉注射含有人vasobibin-1基因的腺病毒可抑制肿瘤生长和肿瘤血管生成。此外，腺病毒人vasohibin-1基因处理的小鼠中剩余的肿瘤血管较小、圆形且成熟，周围有壁细胞。在顺铂治疗中添加腺病毒人 vasobibin-1 基因可提高顺铂在小鼠体内的抗肿瘤活性。这些结果表明内源性vasohibin-1不仅参与肿瘤血管生成，而且当外源性充足时；提供vasohibin-1，它阻断肿瘤的萌芽血管生成，使剩余血管成熟，并增强常规化疗的抗肿瘤效果。 (Am J Pathol 2009, 175:430-439; DOI: 10.2353/ajpath.2009.080788)
In this study, we characterized the significance of the vascular endothelial growth factor-inducible angiogenesis inhibitor vasohibin-1 to tumors. In pathological sections of non-small cell lung carcinoma, vasohibin-1 was present in the endothelial cells of blood vessels of the tumor stroma, but not in the lymphatics. In cancer cells, the presence of vasohibin-1 was associated with hypoxia-inducible factor 1 alpha/vascular endothelial growth factor and fibroblast growth factor-2 expression. We then examined the function of vasohibin-1 in the mouse by subcutaneously inoculating with Lewis lung carcinoma cells. Resultant tumors in vasobibin-1(-/-) mice contained more immature blood vessels and fewer apoptotic tumor cells than tumors in wild-type mice. in wild-type mice that had been inoculated with Lewis lung carcinoma cells, tail vein injection of adenovirus containing the human vasobibin-1 gene inhibited tumor growth and tumor angiogenesis. Moreover, the remaining tumor vessels in adenoviral human vasohibin-1 gene-treated mice were small, round, and mature, surrounded by mural cells. The addition of adenoviral human vasobibin-1 gene to cisplatin treatment improved cisplatin's antitumor activity in mice. These results suggest that endogenous vasohibin-1 is not only involved in tumor angiogenesis, but when sufficient exogenous; vasohibin-1 is supplied, it blocks sprouting angiogenesis by tumors, matures the remaining vessels, and enhances the antitumor effect of conventional chemotherapy. (Am J Pathol 2009, 175:430-439; DOI: 10.2353/ajpath.2009.080788)