Angiopoietin switching regulates angiogenesis and progression of human hepatocellular carcinoma
Angiopoietin switching regulates angiogenesis and progression of human hepatocellular carcinoma
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DOI：
10.1136/jcp.56.11.854
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发表时间：
2003-11-01
影响因子：
3.4
通讯作者：
Tsuneyoshi, M
中科院分区：
文献类型：
--
作者：
Sugimachi, K;Tanaka, S;Tsuneyoshi, M
目的：血管生成素1 （Angiopoietin 1）及其拮抗剂Angiopoietin 2 （ang2）是调节Tie2受体的新型配体。ang2基因在人肝细胞癌（HCC）的高血管型中表达上调。为了更好地了解Ang - Tie2系统在HCC中的作用，我们在一系列人类HCC中研究了这些基因的表达。方法：观察9例正常肝组织和52例手术切除的肝癌组织中血管生成素和Tie2蛋白的表达。此外，我们还研究了缺氧刺激对Hep3B细胞中Ang-1、Ang-2、血管内皮生长因子（VEGF）和促红细胞生成素（EPO）表达的影响。结果：正常肝脏中ang1的表达频率高于ang2。Ang-1在68%的hcc中表达，而Ang-2在81%的hcc中表达，并且在以高血管性为特征的低分化hcc中表达明显更高（p = 0.02），在盆腔改变的肿瘤中表达（p = 0.02）。肿瘤血管中Tie2的强表达与Ang-2表达一致。在Hep3B细胞中，缺氧刺激上调VEGF和EPO，但不上调Ang-1或Ang-2。结论：这些数据支持了Ang-1和Ang-2表达逆转在HCC血管生成和去分化过程中起重要作用的证据。与VEGF不同，在人HCC细胞中，缺氧刺激与ang2上调无关。
Aim: Angiopoietin 1 (Ang-1) and its antagonist, angiopoietin 2 (Ang-2), are novel ligands that regulate the Tie2 receptor. The Ang-2 gene is upregulated in the hypervascular type of human hepatocellular carcinoma (HCC). To gain a better understanding of the role of the Ang - Tie2 system in HCC the expression of these genes was investigated in a series of human HCCs.Methods: The expression of the angiopoietin and Tie2 proteins was investigated in nine normal liver tissues and 52 surgically resected HCCs. In addition, the effects of hypoxic stimuli on Ang-1, Ang-2, vascular endothelial growth factor ( VEGF), and erythropoietin (EPO) expression was investigated in Hep3B cells.Results: Ang-1, rather than Ang-2, was more frequently expressed in the normal liver. Ang-1 was expressed in 68% of HCCs, whereas Ang-2 was expressed in 81%, and was significantly higher in poorly differentiated HCCs characterised by high vascularity ( p = 0.02), and in tumours with a peliotic change ( p = 0.02). Strong expression of Tie2 was seen in tumour vessels in accordance with Ang-2 expression. In Hep3B cells, hypoxic stimuli upregulated VEGF and EPO, but not Ang-1 or Ang-2.Conclusions: These data support the evidence that the reversal of Ang-1 and Ang-2 expression plays an important role in the angiogenic and dedifferentiation processes in HCC. The hypoxic stimuli were not responsible for Ang-2 upregulation, unlike that of VEGF, in human HCC cells.