The role of Twist1 in hepatocellular carcinoma angiogenesis: a clinical study
The role of Twist1 in hepatocellular carcinoma angiogenesis: a clinical study
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Twist1 在肝细胞癌血管生成中的作用：临床研究
DOI：
10.1016/j.humpath.2010.03.010
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发表时间：
2011-06-01
期刊：
影响因子：
3.3
通讯作者：
Sun, Bao-cun
中科院分区：
文献类型：
--
作者：
Che, Na;Zhao, Xiu-lan;Sun, Bao-cun
上皮-间质转化调节因子Twist 1与人肝细胞癌的肿瘤侵袭、转移和血管源性模拟形成有关。然而，Twist 1表达与内皮依赖性血管生成之间的关系尚不清楚。本研究为探讨Twist 1在肝细胞癌血管生成中的作用，采用CD31免疫组化染色法测定微血管密度，探讨微血管密度作为血管生成指标的作用。97例患者石蜡切片微血管密度与Twist 1表达上调相关。免疫组化染色也发现了核迁移，在肝细胞癌转移和预后中表现出重要的临床模式。Twist1的表达与基质金属蛋白酶9的上调有关，Twist1既位于细胞质中，又位于细胞核中；基质金属蛋白酶2在肝细胞癌中没有表现出这些作用。对微血管密度的评估可以提供组织血管生成活性程度的估计，以及其与Twistl上调表达的关系。据我们所知，Twist 1不仅与肿瘤细胞转移有关，而且血管生成模仿也与微血管密度显著相关；这一过程还与基质金属蛋白酶9的上调表达有关。这项工作为Twist I在肝细胞癌血管生成和转移中的作用提供了更好的理解，表明我们的发现可以代表肿瘤细胞上皮-间质转化和内皮依赖性血管生成，正如我们在肝细胞癌中看到的那样。爱思唯尔公司版权所有版权所有。
The epithelial-mesenchymal transition regulator Twist 1 has been implicated in tumor invasion, metastasis, and vasculogenic mimicry formation of human hepatocellular carcinoma. However, the relationship between Twist 1 expression and endothelium-dependent angiogenesis is not clear. In this study, to investigate the role of Twist 1 in hepatocellular carcinoma angiogenesis, we measured the microvessel density by CD31 immunohistochemistry stain and explored the microvessel density as an angiogenesis indicator. The microvessel density in paraffin sections from 97 patients was correlated with Twist 1 expression up-regulation. Nuclear relocation was also identified based on immunohistochemistry stain, presenting a significant clinical pattern in hepatocellular carcinoma metastasis and prognosis. Twist1 expression, which is both located in the cytoplasm and relocated into the nucleus, was associated with matrix metalloproteinase 9 up-regulation; matrix metalloproteinase 2 did not appear to present these effects in hepatocellular carcinoma. An assessment of microvessel density could provide an estimate of the degree of angiogenic activity in tissues, as well as its association with Twistl up-regulated expression. To the best of our knowledge, not only is Twist 1 related to metastasis by tumor cells, but vasculogenic mimicry is also significantly related to microvessel density; this process is also associated with matrix metalloproteinase 9 up-regulated expression. This work provides a better understanding of the role of Twist I in hepatocellular carcinoma angiogenesis and metastasis, suggesting that our findings could represent tumor cell epithelial-mesenchymal transition and endothelium-dependent angiogenesis, as can be seen in hepatocellular carcinoma. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.