Adwan Hassan, Georges Rania, Pervaiz Asim, Berger Martin R
Faculty of Pharmacy and Biotechnology, Department of Pharmacology and Toxicology, The German University in Cairo, Cairo, Egypt.
Toxicology and Chemotherapy Unit, German Cancer Research Center, Heidelberg, Germany.
Front Oncol. 2017 Jul 18;7:152. doi: 10.3389/fonc.2017.00152. eCollection 2017.
Liver is the main target of colorectal cancer (CRC) metastasis. Currently, the number of reports is small, which describe changes in gene expression supporting liver metastasis. Here, a rat model was used for analyzing mRNA modulations during liver colonization and compared with available literature. In the model, CC531 rat CRC cells were injected a mesenteric vein into isogenic WAG/Rij rats and re-isolated at early, intermediate, advanced, and terminal stages of liver colonization. These cells were used for RNA isolation. Microarrays were used for analyzing mRNA profiles of expression. The number of deregulated genes is comparatively large and only part of it has been studied so far. As reported to date, claudins and insulin-like growth factor-binding proteins (IGFBPs) were found to be deregulated. The fact that the chosen method is efficient is confirmed by the study of claudins and IGFBPs, which show altered expression in the initial stages of liver colonization and then return to normalcy. In addition, cadherin was described to be downregulated in epithelial-mesenchymal transition models. It can, therefore, be concluded that the models used are helpful in finding genes, which are instrumental for metastatic liver colonization.
肝脏是结直肠癌（CRC）转移的主要靶器官。目前，描述支持肝转移的基因表达变化的报告数量较少。在此，使用大鼠模型分析肝脏定植过程中的mRNA调节，并与现有文献进行比较。在该模型中，将CC531大鼠结直肠癌细胞经肠系膜静脉注射到同基因的WAG/Rij大鼠体内，并在肝脏定植的早期、中期、晚期和终末期重新分离这些细胞。这些细胞用于RNA提取。利用微阵列分析表达的mRNA谱。失调基因的数量相对较多，到目前为止仅对其中一部分进行了研究。迄今为止的报道表明，紧密连接蛋白和胰岛素样生长因子结合蛋白（IGFBPs）失调。对紧密连接蛋白和IGFBPs的研究证实了所选方法的有效性，它们在肝脏定植的初始阶段表达发生改变，随后恢复正常。此外，在上皮-间质转化模型中，钙黏蛋白被描述为下调。因此，可以得出结论，所使用的模型有助于发现对转移性肝脏定植有重要作用的基因。
