Expression of vascular endothelial growth factor in human hepatocellular carcinoma
Expression of vascular endothelial growth factor in human hepatocellular carcinoma
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DOI：
10.1002/hep.510280111
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发表时间：
1998-07-01
期刊：
影响因子：
13.5
通讯作者：
Kojiro, M
中科院分区：
文献类型：
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作者：
Yamaguchi, R;Yano, H;Kojiro, M
血管内皮生长因子（VEGF）被认为在肿瘤血管生成中起重要作用。本研究采用免疫组织化学方法检测了不同组织学分级和大小的肝细胞癌（HCC）中VEGF的表达。在由单一组织学分级的癌组织组成的HCC中，VEGF表达在高分化HCC中最高，其次是中分化HCC，然后是低分化HCC。随着肿瘤大小的增加，VEGF阳性率逐渐降低。在大于3.0cm的结节中，VEGF阴性率为36.8%。在由两种不同组织学分级的癌组织组成的HCC中，在较高级别的HCC组分中表达较低。VEGF在肉瘤组织中不表达，而在癌旁组织中表达。在炎性细胞浸润明显的非癌组织中表达也明显。VEGF的表达也在六个肝癌细胞系进行了检查。逆转录聚合酶链反应（RT-PCR）分析显示，两种分泌型（VEGF（121）和VEGF（165））的表达最高。因此，通过使用酶联免疫吸附测定（ELISA）在有或没有炎性细胞因子的情况下测量培养上清液中的VEGF蛋白，即，白细胞介素（IL）-1 β、干扰素（IFN）-α、IFN-γ和肿瘤坏死因子（TNF）-α;和生长因子，即，表皮生长因子（EGF）、血小板衍生生长因子（PDGF）-BB、碱性成纤维细胞生长因子（bFGP）和转化生长因子（TGF）-α。结果，VEGF从细胞系的分泌在不同程度上上调。基于这些发现，VEGF在HCC组织中的表达被认为与组织学分级有关。这些发现还表明，多种细胞因子和生长因子可以协同作用，以提高VEGF在HCC中的表达。
Vascular endothelial growth factor (VEGF) is thought to take an important role in tumor angiogenesis. The present study examined VEGF expression immunohistochemically in hepatocellular carcinomas (HCCs) in various histological grades and sizes. In HCCs that were composed of cancerous tissues of single histological grade, VEGF expression was the highest in well-differentiated HCCs, followed by moderately differentiated HCCs, and then poorly differentiated HCCs. VEGF positivity gradually decreased with the increase in tumor size. In the nodules larger than 3.0 cm, 36.8% were VEGF-negative. In HCCs consisting of cancerous tissues of two different histological grades, the expression was less intensive in the higher-grade HCC component. VEGF was not expressed in sarcomatous areas, while VEGF was expressed in the surrounding HCC tissues. The expression was also remarkable in the noncancerous tissues in which inflammatory cell infiltration was apparent. VEGF expression was also examined in six HCC cell lines. In reverse-transcription polymerase chain reaction (RT-PCR) analysis, expressions of the two secretion types (VEGF(121) and VEGF(165)) were the highest. Thus, VEGF protein in culture supernatant was measured by using enzyme-linked immunosorbent assay (ELISA) with or without inflammatory cytokines, i.e., interleukin (IL)-1 beta, interferon (IFN)-alpha, IFN-gamma, and tumor necrosis factor (TNF)-alpha; and growth factors, i.e., epidermal growth factor (EGF), platelet-derived growth factor (PDGF)-BB, basic fibroblast growth factor (bFGP), and transforming growth factor (TGF)-alpha. As a result, secretion of VEGF from the cell lines was upregulated at various degrees. Based on these findings, VEGF expression in HCC tissues was thought to be related to the histological grade. The findings also indicate that various cytokines and growth factors could cooperatively act to enhance VEGF expressions in HCC.