Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China (mainland).
Shanghai Institute of Medical Imaging, Shanghai, China (mainland).
Med Sci Monit. 2019 Nov 18;25:8694-8703. doi: 10.12659/MSM.917648.
BACKGROUND This study aimed to develop a nude mouse model of orthotopic liver transplantation of HCCLM3 human hepatocellular carcinoma (HCC) cell xenografts and the use of imaging and histology to evaluate tumor development and progression. MATERIAL AND METHODS HCCLM3 cells were injected subcutaneously into 25 healthy male athymic BALB/c (nu/nu) nude mice. The tumors that developed were transplanted into the liver of a new set of nude mice. After four weeks and six weeks, the mice were imaged using ultrasound (US), software-assisted contrast-enhanced ultrasound (CEUS), fluorodeoxyglucose-positron emission tomography (FDG-PET). Histology was performed on the liver and liver tumors, and included immunohistochemistry for vascular endothelial growth factor (VEGF), CD31, CD34, and alpha-smooth muscle actin (alpha-SMA). RESULTS The success rate for orthotopic tumor transplantation in the mouse liver was 90% (18/20). Liver tumors measured 11.8±2.6 mm in diameter and 525.9±250.8 mm3 in volume on the sixth week. CEUS showed rapid wash-in and washout in the liver tumors, and PET showed low tumor cell metabolism. Bone metastases were present in 45% (9/20) of mice in the sixth week. Immunohistochemistry showed positive expression for VEGF, CD31, CD34, and alpha-SMA. CONCLUSIONS The nude mouse orthotopic liver transplantation model of human HCC was shown to be a reliable model that has the potential for future research on the pathogenesis and progression of HCC and studies on drug development.
本研究旨在建立人肝癌细胞系 HCCLM3 裸鼠原位肝移植模型，并利用影像学和组织学方法评估肿瘤的发生和进展。
将 HCCLM3 细胞皮下注射入 25 只健康雄性无胸腺 BALB/c（nu/nu）裸鼠体内。待肿瘤生长后，将其移植到另一批裸鼠的肝脏中。在四周和六周时，使用超声（US）、软件辅助的超声造影（CEUS）、氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）对小鼠进行成像。对肝脏和肝肿瘤进行组织学检查，包括血管内皮生长因子（VEGF）、CD31、CD34 和α-平滑肌肌动蛋白（α-SMA）的免疫组织化学染色。
裸鼠肝内原位肿瘤移植的成功率为 90%（18/20）。第六周时，肝脏肿瘤的直径为 11.8±2.6mm，体积为 525.9±250.8mm3。CEUS 显示肝脏肿瘤快速的增强和廓清，PET 显示肿瘤细胞代谢率较低。第六周时，45%（9/20）的小鼠出现骨转移。免疫组织化学染色显示 VEGF、CD31、CD34 和α-SMA 呈阳性表达。
人肝癌裸鼠原位肝移植模型是一种可靠的模型，具有研究肝癌发病机制和进展以及药物开发的潜力。
