She Qin, Hu Shuya, Pu Xia, Guo Qingxi, Mou Chunru, Yang Chengwan
Department of Pathology, The Affliated Hospital of Southwest Medical University Luzhou, Sichuan Province, China.
Department of Pathology, Sichuan Mianyang 404 Hospital Mianyang, Sichuan Province, China.
Am J Cancer Res. 2020 Dec 1;10(12):4198-4210. eCollection 2020.
Vasculogenic Mimicry (VM) is the main source of blood supply in the early stage of tumor growth. Carcinoma-associated fibroblasts (CAFs) are one of the most important host cells in the tumor microenvironment. Some studies have found that CAFs can promote tumor angiogenesis, but there are few reports on the relationship between CAFs and VM. Tissue samples were collected from 60 cases of hepatocellular carcinoma (HCC) and 10 persons with normal liver function. The relationship between VM expression and clinicopathologic features was analyzed. Furthermore, the relationship between VM expression and vimentin or α-SMA expression was analyzed. Primary culture of hepatocellular CAFs and the collection of conditioned media were carried out. The effects of hepatocellular CAF conditioned medium on the formation of VM and the levels of VM-related proteins and genes in MHCC-97H cells were studied. The positive rate of VM was 35.0% in HCC tissues. There was no VM expression in normal liver tissues. VM expression was related to tumor diameter, Edmondson grade, clinical stage, and liver cirrhosis. The expression of vimentin and α-SMA in VM-positive patients was higher than in VM-negative patients. Different concentrations of hepatocellular CAF conditioned medium could promote the formation of VM and increase the expression of VM-related genes and proteins (MMP2 and EphA2) in MHCC-97H cells. The results show that there was a significant correlation between VM formation and the expression of vimentin or α-SMA in HCC tissues. The conditioned medium of hepatocellular CAFs may promote VM formation and the expression of VM-related genes and proteins (MMP2 and EphA2) in hepatoma cell line MHCC-97H.
血管生成拟态（VM）是肿瘤生长早期的主要血供来源。癌相关成纤维细胞（CAFs）是肿瘤微环境中最重要的宿主细胞之一。一些研究发现，CAFs可促进肿瘤血管生成，但关于CAFs与VM之间关系的报道较少。收集60例肝细胞癌（HCC）组织样本和10例肝功能正常者的组织样本。分析VM表达与临床病理特征之间的关系。此外，分析VM表达与波形蛋白或α-SMA表达之间的关系。进行肝细胞CAFs的原代培养及条件培养基的收集。研究肝细胞CAF条件培养基对MHCC-97H细胞中VM形成以及VM相关蛋白和基因水平的影响。HCC组织中VM阳性率为35.0%。正常肝组织中无VM表达。VM表达与肿瘤直径、Edmondson分级、临床分期及肝硬化有关。VM阳性患者中波形蛋白和α-SMA的表达高于VM阴性患者。不同浓度的肝细胞CAF条件培养基可促进MHCC-97H细胞中VM的形成，并增加VM相关基因和蛋白（MMP2和EphA2）的表达。结果表明，HCC组织中VM形成与波形蛋白或α-SMA的表达之间存在显著相关性。肝细胞CAFs的条件培养基可能促进肝癌细胞系MHCC-97H中VM的形成以及VM相关基因和蛋白（MMP2和EphA2）的表达。
