Harada T, Arii S, Mise M, Imamura T, Higashitsuji H, Furutani M, Niwano M, Ishigami S, Fukumoto M, Seiki M, Sato H, Imamura M
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
J Hepatol. 1998 Feb;28(2):231-9. doi: 10.1016/0168-8278(88)80010-2.
BACKGROUND/AIMS: The matrix metalloproteinase (MMP) family play important roles in the invasion of cancer cells by degrading the extracellular matrices. The current study was designed to determine the expression pattern of membrane-type matrix metalloproteinase-1 (MT1-MMP) in hepatocellular carcinomas and its participation in invasion potential.
MT1-MMP mRNA expression was examined in 25 human hepatocellular carcinoma specimens using Northern blot, and the correlation to clinicopathological features was evaluated. In situ hybridization and immunohistochemistry were performed to study the localization and the cells responsible for the production.
Northern blot analysis revealed high levels of MT1-MMP mRNA expression in tumorous portions in all cases, whereas in non-tumorous portions moderate or faint expression was evident in 22/25 cases. In 21/25 cases, the expression levels in tumorous portion were higher than those in non-tumorous portion. In particular, hepatocellular carcinoma with capsule infiltration demonstrated significantly higher expression than those without (p<0.05). In situ hybridization and immunohistochemical study revealed MT1-MMP transcripts and proteins in cancer cells and stromal cells, respectively. MT1-MMP positive cells were preferentially observed in the invading border of tumor nests. The MMP-2 transcript showed a similar pattern to that of MT1-MMP by in situ hybridization.
The present study showed that the MT1-MMP gene is strongly expressed in hepatocellular carcinoma cells and is involved in the invasion potential of hepatocellular carcinoma, and also that MT1-MMP may be one of the key molecules responsible for the invasion potential of hepatocellular carcinoma. Furthermore, the evidence suggests that MT1-MMP and MMP-2 cooperate in the process of cancer invasion.
背景/目的：基质金属蛋白酶（MMP）家族通过降解细胞外基质在癌细胞侵袭中发挥重要作用。本研究旨在确定膜型基质金属蛋白酶-1（MT1-MMP）在肝细胞癌中的表达模式及其在侵袭潜能中的作用。
采用Northern印迹法检测25例人肝细胞癌标本中MT1-MMP mRNA的表达，并评估其与临床病理特征的相关性。进行原位杂交和免疫组化研究以确定其定位及产生MT1-MMP的细胞。
Northern印迹分析显示，所有病例的肿瘤组织中MT1-MMP mRNA表达水平均较高，而在25例中的22例非肿瘤组织中可见中度或微弱表达。25例中的21例，肿瘤组织中的表达水平高于非肿瘤组织。特别是，有包膜浸润的肝细胞癌的表达明显高于无包膜浸润者（p<0.05）。原位杂交和免疫组化研究分别在癌细胞和基质细胞中发现了MT1-MMP转录本和蛋白。MT1-MMP阳性细胞在肿瘤巢的侵袭边缘优先被观察到。原位杂交显示MMP-2转录本与MT1-MMP的转录本呈现相似模式。
本研究表明MT1-MMP基因在肝癌细胞中强烈表达，并参与肝细胞癌的侵袭潜能，MT1-MMP可能是肝细胞癌侵袭潜能的关键分子之一。此外，有证据表明MT1-MMP和MMP-2在癌症侵袭过程中协同作用。
