Tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 potentates the anchorage-independent growth of human hepatoma HepG2 cells
Tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 potentates the anchorage-independent growth of human hepatoma HepG2 cells
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DOI：
10.1016/j.lfs.2007.06.002
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发表时间：
2007-07-04
期刊：
影响因子：
6.1
通讯作者：
Aoyagi, Yutaka
中科院分区：
文献类型：
--
作者：
Hokari, Mariko;Matsuda, Yasunobu;Aoyagi, Yutaka
癌胚抗原相关细胞黏附分子1(CEACAM1)是免疫球蛋白超家族的一种黏附分子，因其在多种侵袭性癌细胞中表达下调，被认为是一种潜在的肿瘤抑制因子。然而，最近的一些研究表明，CEACAM1在某些类型的肿瘤细胞中起积极的恶性进展或迁移作用，这表明CEACAM1在不同类型的癌细胞中的作用可能是不同的。为了探讨CEACAM1在肝细胞癌中表达的功能后果，我们分析了CEACAM1在肝癌细胞系HLF、PLC/PRF/5、HepG2和KYN-2中的表达情况。我们发现CEACAM1只在HepG2细胞中表达，表现出促进锚定非依赖性生长的独特性质。当针对CEACAM1的小干扰RNA作用于HepG2细胞时，细胞在单层培养中的生长速度加快。相反，在悬浮培养条件下，抑制CEACAM1的表达显著降低了细胞的生长速度，抑制了细胞与细胞的附着速度。透明质酸酶处理使悬浮培养的HepG2细胞生长速度减弱，表明细胞-细胞贴壁是非贴壁生长所必需的。我们的数据可能揭示了CEACAM1在肝癌发生中的双重作用，这表明在锚定依赖的生长条件下，CEACAM1在HepG2细胞中发挥肿瘤抑制作用，而在锚定非依赖的生长条件下，CEACAM1通过增强细胞与细胞的附着来促进细胞增殖。(C)2007 Elsevier Inc.保留所有权利。
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), an adhesion molecule of the immunoglobulin superfamily, has been characterized as a putative tumor suppressor because it is frequently down-regulated in aggressive types of cancer cells. Recently, however, several studies have shown that CEACAM 1 actively contributes to malignant progression or migration in some types of tumor cells, suggesting that the role of CEACAM 1 might be diverse among different types of cancer cells. To investigate the functional consequences of CEACAM 1 expression in hepatocellular carcinoma, we analyzed the status of CEACAM 1 in hepatoma cell lines HLF, PLC/PRF/5, HepG2 and KYN-2. We found that CEACAM1 was only expressed in HepG2 cells, which show a unique property for enhanced anchorage-independent growth. When HepG2 cells were treated with small interfering RNA targeted against CEACAM1, the growth rate in monolayer culture was increased. In contrast, when HepG2 cells were cultured in suspension, inhibition of CEACAM1 expression significantly decreased the growth rate, and the speed of cell-cell attachment was repressed. Hyaluronidase treatment attenuated the growth rate of HepG2 cells in suspension culture, indicating that cell-cell attachment is a requisite for anchorage-independent growth. Our data may reveal the dual role of CEACAM1 on hepatocarcinogenesis, by showing that CEACAM1 acts as a tumor suppressor in HepG2 cells in anchorage-dependent growth conditions, while in anchorage-independent growth conditions, it augments cell proliferation by potentiating the cell-cell attachment. (c) 2007 Elsevier Inc. All rights reserved.