CEINGE Biotecnologie Avanzate, Naples, Italy.
Mol Med. 2010 Mar;16(3-4):102-15. doi: 10.2119/molmed.2009.00119. Epub 2009 Dec 21.
Hepatocellular carcinoma is one of the most common cancers worldwide. Despite several efforts to elucidate hepatocellular carcinoma molecular pathogenesis, it is still not fully understood. To acquire further insights into the molecular mechanisms of hepatocellular carcinoma, we performed a systematic functional genomic approach on human HuH-7 and JHH-6 cells. The subsequent analysis of the differentially expressed genes in human specimens revealed a molecular signature of 11 genes from which we selected the LGALS1 gene, which was overexpressed in hepatocellular carcinoma. The expression analysis in humans of Galectin-1 (Gal-1), the protein encoded by LGALS1, showed a Gal-1 preferential accumulation in the stromal tissue around hepatocellular carcinoma tumors. Moreover, a significant association between increased expression of Gal-1 in hepatocellular carcinoma and the presence of metastasis was observed. Interestingly, Gal-1 overexpression resulted in an increase of cell migration and invasion. In conclusion, this study provides a portfolio of targets useful for future investigations into molecular marker-discovery studies on a large number of patients and functional assays. In addition, our data provide evidence that Gal-1 plays a role in hepatocellular carcinoma cell migration and invasion, and we suggest that further studies should be conducted to fully establish the role of Gal-1 in hepatocellular carcinoma pathogenesis and evaluate Gal-1 as a potential molecular therapeutic target.
肝细胞癌是全球最常见的癌症之一。尽管已经做出了许多努力来阐明肝细胞癌的分子发病机制,但仍未完全了解。为了更深入地了解肝细胞癌的分子机制,我们对人 HuH-7 和 JHH-6 细胞进行了系统的功能基因组方法。对人标本中差异表达基因的后续分析揭示了 11 个基因的分子特征,我们从中选择了 LGALS1 基因,该基因在肝细胞癌中过度表达。Galectin-1(Gal-1)的表达分析,即 LGALS1 编码的蛋白质,显示 Gal-1 在肝细胞癌肿瘤周围的基质组织中优先积累。此外,还观察到 Gal-1 在肝细胞癌中的表达增加与转移的存在之间存在显著相关性。有趣的是,Gal-1 的过表达导致细胞迁移和侵袭增加。总之,这项研究提供了一组有用的靶点,可用于对大量患者进行分子标志物发现研究和功能测定的未来研究。此外,我们的数据表明 Gal-1 在肝细胞癌细胞迁移和侵袭中发挥作用,我们建议进行进一步的研究以充分确定 Gal-1 在肝细胞癌发病机制中的作用,并评估 Gal-1 作为潜在的分子治疗靶标。