Osteoactivin expressed during cirrhosis development in rats fed a choline-deficient, L-amino acid-defined diet, accelerates motility of hepatoma cells
Osteoactivin expressed during cirrhosis development in rats fed a choline-deficient, L-amino acid-defined diet, accelerates motility of hepatoma cells
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DOI：
10.1016/s0168-8278(03)00361-1
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发表时间：
2003-11-01
影响因子：
25.7
通讯作者：
Tsubouchi, H
中科院分区：
文献类型：
--
作者：
Onaga, M;Ido, A;Tsubouchi, H
背景/目的：肝细胞癌（HCC）与慢性肝病，特别是肝硬化密切相关。然而，在发展为肝硬化的情况下参与肝癌发生的基因仍然未知。本研究旨在鉴定与早期肝硬化相关肝癌发生相关的基因。方法：我们使用抑制消减杂交技术检查了正常大鼠和喂食缺乏胆碱、L-氨基酸限定（CDAA）饮食的大鼠肝脏之间差异表达的基因。我们检测了本次筛选中分离出的骨激活素 (OA) 在肝脏和 HCC 组织中的表达及其对侵袭和转移的影响。结果：在喂食 CDAA 饮食 1-3 个月的大鼠的肝脏中，OA mRNA 强烈表达。中度表达持续18个月。 OA过表达增加了大鼠肝癌细胞体外和体内的侵袭性和转移性。在人类中，正常肝组织中未检测到 OA 表达。虽然在 HCC 周围的肝硬化非肿瘤性肝组织中可检测到 OA 转录本，但大多数 HCC 组织样本表现出比周围正常组织更高水平的 OA 表达。结论：这些结果表明 OA 是通过刺激肿瘤侵袭性和转移潜力参与 HCC 进展的新因素。 (C) 2003 年欧洲肝脏研究协会。由 Elsevier B.V. 出版。保留所有权利。
Background/Aims: Hepatocellular carcinoma (HCC) is closely associated with chronic liver diseases, particularly cirrhosis. However, the genes involved in hepatocarcinogenesis in the context of developing cirrhosis remain unknown. This study aims to identify genes associated with early cirrhosis-associated hepatocarcinogenesis.Methods: We examined genes differentially expressed between the livers of normal rats and rats fed a choline-deficient, L-amino acid-defined (CDAA) diet using suppression subtractive hybridization. We examined both the expression in the liver and HCC tissues of osteoactivin (OA), isolated in this screen, and its effect on invasiveness and metastasis.Results: OA mRNA was strongly expressed in the livers of rats fed the CDAA diet for 1-3 months. Moderate expression was sustained for 18 months. OA overexpression increased the invasiveness and metastasis of rat hepatoma cells in vitro and in vivo. In humans, OA expression was not detectable in normal liver tissues. While OA transcripts were detectable in cirrhotic nontumorous liver tissues surrounding HCCs, the majority of HCC tissue samples exhibited higher levels of OA expression than the surrounding normal tissue.Conclusions: These results indicate that OA is a novel factor involved in the progression of HCC via stimulation of tumor invasiveness and metastatic potential. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.