Ebara M, Fukuda H, Hatano R, Saisho H, Nagato Y, Suzuki K, Nakajima K, Yukawa M, Kondo F, Nakayama A, Sakurai H
First Department of Medicine, School of Medicine, Chiba University, Japan.
J Hepatol. 2000 Sep;33(3):415-22. doi: 10.1016/s0168-8278(00)80277-9.
BACKGROUND/AIM: Accumulation of copper (Cu) in hepatocellular carcinoma (HCC), especially in small tumors, is greater than that in the surrounding liver parenchyma. Metallothionein (MT) is considered to be present as Cu-MT, Zn,Cu-MT or Zn-MT. The aim of this study was to determine the presence and localization of Cu-MT and Zn-MT in HCC and surrounding liver parenchyma.
In 16 HCC patients, surgically resected specimens including HCC and surrounding liver parenchyma were evaluated.
The level of Cu present in small HCC (<4 cm in diameter) was significantly greater than that in the surrounding liver parenchyma (p<0.05). However, the level of Cu in large HCC (>4 cm in diameter) was similar to that in the surrounding liver parenchyma. Analysis by Sephadex G-75 gel filtration revealed that the peak fraction due to Cu was identical to that due to MT in 14 (87.5%) of 16 HCC, the peak fraction due to Cu and Zn was identical to that due to MT in 2 (12.5%) HCC, and the peak fraction due to Zn was identical to that of MT in none of 16 HCC.
Accumulation of Cu in small HCC, in which Cu was present as Cu-MT or Zn, Cu-MT, was greater than that in the surrounding liver parenchyma. Cu accumulation and the presence of MT in the liver may be related to carcinogenesis of HCC, because of the similarity of these findings in the experimental data of Long-Evans rats with a cinnamon-like coat color who develop HCC spontaneously.
背景/目的:肝细胞癌(HCC)中铜(Cu)的蓄积,尤其是在小肿瘤中,大于周围肝实质中的铜蓄积。金属硫蛋白(MT)被认为以铜-金属硫蛋白(Cu-MT)、锌铜-金属硫蛋白(Zn,Cu-MT)或锌-金属硫蛋白(Zn-MT)的形式存在。本研究的目的是确定Cu-MT和Zn-MT在HCC及周围肝实质中的存在情况和定位。
对16例HCC患者手术切除的包括HCC及周围肝实质的标本进行评估。
小HCC(直径<4 cm)中的铜水平显著高于周围肝实质(p<0.05)。然而,大HCC(直径>4 cm)中的铜水平与周围肝实质相似。通过Sephadex G-75凝胶过滤分析发现,16例HCC中有14例(87.5%)铜的峰值组分与MT的峰值组分相同,2例(12.5%)HCC中铜和锌的峰值组分与MT的峰值组分相同,16例HCC中锌的峰值组分与MT的峰值组分均不相同。
小HCC中以Cu-MT或Zn,Cu-MT形式存在的铜蓄积大于周围肝实质中的铜蓄积。肝脏中铜的蓄积和MT的存在可能与HCC的致癌作用有关,因为这些发现与自发发生HCC的肉桂色被毛Long-Evans大鼠的实验数据相似。