Expression of hepatoma-derived growth factor in hepatocarcinogenesis
Expression of hepatoma-derived growth factor in hepatocarcinogenesis
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DOI：
10.1046/j.1440-1746.2003.03191.x
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发表时间：
2003-11-01
影响因子：
4.1
通讯作者：
Kawase, I
中科院分区：
文献类型：
--
作者：
Yoshida, K;Nakamura, H;Kawase, I
背景与目的：本研究在两种啮齿类动物模型中研究了人肝细胞癌（HCC）和肝癌发生过程中肝脏中肝细胞源性生长因子（HDGF）的表达。方法：采用Northern blotting和免疫组化方法分析人和啮齿类动物模型中HDGF的表达。结果：肝细胞源性生长因子的表达水平较高。 Northern blotting显示，在患有肝炎的人中，HCC中的表达高于邻近肝脏中的表达。使用特异性抗 HDGF 抗体的免疫组织化学显示，与邻近的正常肝细胞相比，HDGF 在 HCC 细胞的细胞核和细胞质中表达更强烈、更频繁。 Northern 印迹和免疫组织化学显示，与脂肪肝 Shionogi (FLS) 小鼠的邻近脂肪肝相比，与缺乏胆碱氨基酸喂养的大鼠的肝硬化肝脏相比，肝癌衍生生长因子在肿瘤中的表达也更强。在FLS小鼠的肝脏中，HDGF表达从出生后24周到52周逐渐增加，表明HDGF表达在肿瘤发生的早期阶段就已经增加。在有脂肪变化的非肿瘤肝脏中，24周龄时出现表达HDGF的灶，这些灶是活化的巨噬细胞簇，具有增强的DNA合成和脂肪滴。提示HDGF从这些病灶分泌或释放，并以旁分泌方式刺激FLS小鼠的肝细胞增殖，并以自分泌方式刺激肝肿瘤细胞的增殖。结论：目前的研究结果表明HDGF在人类和啮齿动物的HCC的发生或进展中发挥重要作用。 (C) 2003 年布莱克威尔出版亚洲有限公司。
Background and Aim: The present study investigated the expression of hepatoma-derived growth factor (HDGF) in human hepatocellular carcinoma (HCC) and in the liver during hepatocarcinogenesis in two rodent models.Methods: Expression of HDGF was analyzed using northern blotting and immunohistochemistry in the human and rodent models.Results: Hepatoma-derived growth factor was more highly expressed in HCC than in the adjacent liver in humans with hepatitis, as shown by northern blotting. Using immunohistochemistry with the specific anti-HDGF antibody, HDGF was more strongly and frequently expressed in the nucleus and cytoplasm of HCC cells than in the adjacent normal hepatocytes. Hepatoma-derived growth factor was also more strongly expressed in the tumors than in the adjacent fatty liver of fatty liver Shionogi (FLS) mice, than in the cirrhotic liver of choline-deficient amino acid feeding rats, as shown by northern blotting and immunohistochemistry. In the liver of FLS mice, HDGF expression increased gradually from the age of 24 weeks through to 52 weeks after birth, showing that HDGF expression was already increased at an early stage before tumor development. In the non-tumorous liver with fatty change, the foci expressing HDGF appeared at 24 weeks of age, which were the activated macrophage clusters with enhanced DNA synthesis and fat droplets. It is suggested that HDGF was secreted or released from these foci and stimulated hepatocyte proliferation in a paracrine manner in FLS mice, and stimulated the proliferation of hepatic tumor cells in an autocrine manner.Conclusions: The present findings suggest that HDGF plays an important role in the development or progression of HCC in humans and rodents. (C) 2003 Blackwell Publishing Asia Pty Ltd.