The mechanism and clinical significance of loss of CEACAM1 expression in hepatocellular carcinoma

癌胚抗原相关细胞粘附分子1（CEACAM 1），免疫球蛋白超家族的粘附分子，已被表征为推定的肿瘤抑制因子，因为它经常在侵袭性类型的癌细胞中下调。然而，最近的一些研究表明，CEACAM 1在某些类型的肿瘤细胞中积极促进恶性进展或迁移，这表明CEACAM 1的作用在不同类型的癌细胞中可能是不同的。为了研究CEACAM 1在肝细胞癌中表达的功能后果，我们分析了肝癌细胞系HLF、PLC/PRF/5、HepG 2和KYN-2中CEACAM 1的状态。我们发现CEACAM 1仅在HepG 2细胞中表达，其显示出增强的锚定非依赖性生长的独特性质。当用针对CEACAM 1的小干扰RNA处理HepG 2细胞时，单层培养中的生长速率增加。相反，当HepG 2细胞悬浮培养时，CEACAM 1表达的抑制显著降低了生长速率，并且细胞-细胞粘附的速度被抑制。透明质酸酶处理减弱了悬浮培养中HepG 2细胞的生长速率，表明细胞-细胞附着是锚定非依赖性生长的必要条件。我们的数据可能揭示了CEACAM 1在肝癌发生中的双重作用，通过显示CEACAM 1在HepG 2细胞中在锚定依赖性生长条件下作为肿瘤抑制因子，而在锚定非依赖性生长条件下，它通过增强细胞-细胞附着来增强细胞增殖。

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 CEACAM1 actively contributes to malignant progression or migration in some types of tumor cells, suggesting that the role of CEACAM1 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 CEACAM1 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.