Torimura T, Sata M, Ueno T, Kin M, Tsuji R, Suzaku K, Hashimoto O, Sugawara H, Tanikawa K
Second Department of Medicine and Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Japan.
Hum Pathol. 1998 Sep;29(9):986-91. doi: 10.1016/s0046-8177(98)90205-2.
Vascular endothelial growth factor is a potent direct-acting angiogenic factor. Early in hepatocarcinogenesis, hepatocellular carcinomas do not show hypervascularity; at later stages, they require abundant arterial blood flow. We investigated the role of vascular endothelial growth factor in hepatocellular carcinoma arterialization. We studied 51 patients with hepatocellular carcinoma. All patients had undergone hepatic arteriography. Vascular endothelial growth factor expression was investigated by immunohistochemistry (n = 51) and in situ hybridization (n = 13), and the changes in vascular endothelial growth factor expression were evaluated in relation to tumor differentiation and changes in tumor vascularity. The expression of vascular endothelial growth factor isoforms in hepatocellular carcinomas was also analyzed by reverse transcriptase-polymerase chain reaction (n = 10). Vascular endothelial growth factor expression was detected in hepatoma cells and hepatic stellate cells, and increased vascular endothelial growth factor expression was associated with tumor dedifferentiation. Vascular endothelial growth factor expression in hypervascular hepatocellular carcinomas was greater than in those not showing hypervascularity. The major vascular endothelial growth factor isoforms expressed in hepatocellular carcinoma were 121 and 165. These findings indicate that vascular endothelial growth factors 121 and 165 play a critical role in the process of angiogenesis in hepatocellular carcinomas.
血管内皮生长因子是一种强效的直接作用血管生成因子。在肝癌发生早期，肝细胞癌不表现出血管增多；在后期，它们需要丰富的动脉血流。我们研究了血管内皮生长因子在肝细胞癌动脉化中的作用。我们研究了51例肝细胞癌患者。所有患者均接受了肝动脉造影。通过免疫组织化学（n = 51）和原位杂交（n = 13）研究血管内皮生长因子表达，并根据肿瘤分化和肿瘤血管变化评估血管内皮生长因子表达的变化。还通过逆转录聚合酶链反应（n = 10）分析了肝细胞癌中血管内皮生长因子异构体的表达。在肝癌细胞和肝星状细胞中检测到血管内皮生长因子表达，血管内皮生长因子表达增加与肿瘤去分化相关。高血管性肝细胞癌中的血管内皮生长因子表达高于未表现出血管增多的肝细胞癌。肝细胞癌中表达的主要血管内皮生长因子异构体是121和165。这些发现表明血管内皮生长因子121和165在肝细胞癌血管生成过程中起关键作用。
