Angiopoietins and Tie-2 expression in angiogenesis and proliferation of human hepatocellular carcinoma
Angiopoietins and Tie-2 expression in angiogenesis and proliferation of human hepatocellular carcinoma
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DOI：
10.1053/jhep.2003.50204
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发表时间：
2003-05-01
期刊：
影响因子：
13.5
通讯作者：
Miyazaki, M
中科院分区：
文献类型：
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作者：
Mitsuhashi, N;Shimizu, H;Miyazaki, M
人肝细胞癌（HCC）是一种血管丰富的肿瘤，但血管生成过程的机制尚未完全了解。血管生成素（Angiopoietins，Ang）是近年来发现的Tie-2受体的配体，在血管生成过程中对血管的成熟和稳定起重要作用。在这项研究中，我们研究了46例HCC患者手术切除标本中Ang-1、Ang-2、Tie-2和血管内皮生长因子（VEGF）的表达，以确定它们在肿瘤血管生成及其进展中的潜在作用。与肝转移患者的正常肝组织相比，HCC中VEGF信使RNA（mRNA）显著上调。HCC与癌旁肝组织之间无差异。与癌旁肝组织相比，HCC组织中Ang-2 mRNA的表达明显增加。而Ang-1和Tie-2 mRNA在HCC中的表达与癌旁肝组织无明显差异。免疫组化染色也显示HCC中Ang-2蛋白表达增加。此外，HCC中高Ang-2/1 mRNA比率与肿瘤门静脉浸润、肿瘤直径和通过CD 34评估的微血管密度水平密切相关。免疫染色。就预后而言，与低Ang-2/1 mRNA比率组相比，高Ang-2/1 mRNA比率组患者的生存时间显著较差。总之，血管内皮生长因子的存在下，血管生成素-2/1的表达增加可能在促进肿瘤血管生成和人类肝癌的进展中发挥关键作用。
Human hepatocellular carcinoma (HCC) is a hypervascular tumor but the mechanisms underlying the process of angiogenesis are not fully understood. Angiopoietins (Ang) have been recently identified as ligands for Tie-2 receptor and are thought to be important factors in vascular maturation and stability during angiogenesis. In this study, we investigated the expression of Ang-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in surgically resected specimens from 46 patients with HCC to determine their potential role in tumor angiogenesis and its progression. VEGF messenger RNA (mRNA) was significantly up-regulated in HCC compared to normal liver tissue from patients with hepatic metastases. No differences were found between HCC and adjacent liver tissue. Meanwhile, Ang-2 mRNA expression in HCC was significantly increased when compared to adjacent liver tissue. On the other hand, Ang-1 and Tie-2 mRNA expression in HCC was not different from that in adjacent liver tissue. Immunohistochemical staining also showed increased Ang-2 protein in HCC. Furthermore, a high Ang-2/1 mRNA ratio in HCC was closely associated with tumor portal vein invasion, tumor diameter, and the microvessel density level as assessed by CD34. Immunostaining. With regard to prognosis, the survival time for patients in the high Ang2/1 mRNA ratio group was significantly poorer when compared with the low Ang-2/1 mRNA ratio group. In conclusion, an increased expression of Ang-2/1 in the presence of VEGF may play a critical role in promoting tumor angiogenesis and progression in human HCC.