Kuriyama S, Yamazaki M, Mitoro A, Tsujimoto T, Kikukawa M, Tsujinoue H, Nakatani T, Toyokawa Y, Yoshiji H, Fukui H
Third Department of Internal Medicine, Nara Medical University, Japan.
Int J Cancer. 1999 Jan 29;80(3):471-6. doi: 10.1002/(sici)1097-0215(19990129)80:3<471::aid-ijc22>3.0.co;2-4.
Prognosis of hepatocellular carcinoma (HCC) still remains poor mainly because of intrahepatic metastasis. In the majority of cases, HCC is found in conjunction with liver cirrhosis. It is, therefore, of great importance to investigate the invasive and metastatic behavior of HCC in cirrhotic liver. To examine this, a liver cirrhosis model was produced by injecting thioacetamide i.p. into mice. Murine HCC cells were labeled with the fluorescent carbocyanine dye, DiI, and implanted directly under the capsule of cirrhotic and normal livers of syngeneic mice. DiI-labeled HCC cells in the liver were observed under fluorescent and confocal microscopy. Histological analysis of cirrhotic and normal livers revealed that implanted HCC cells migrated to and invaded the adjacent periportal regions, but not the adjacent centrolobular areas. This characteristic behavior of HCC was more evident in cirrhotic liver than in normal liver. Furthermore, intrahepatic metastasis to unimplanted hepatic lobes was observed in cirrhotic liver as early as 7 days after implantation, while it was not detected in normal liver even 4 weeks later. Thus, an orthotopic animal model for HCC with cirrhosis described here may be suitable for investigating the invasive and metastatic behavior of HCC. Importantly, labeling tumor cells with a fluorescent dye before orthotopic implantation may be a convenient and useful method to investigate the invasive and metastatic behavior of various types of cancer.
肝细胞癌（HCC）的预后仍然很差，主要原因是肝内转移。在大多数情况下，HCC是在肝硬化的基础上发现的。因此，研究HCC在肝硬化肝脏中的侵袭和转移行为具有重要意义。为了对此进行研究，通过腹腔注射硫代乙酰胺给小鼠建立肝硬化模型。将鼠源HCC细胞用荧光碳菁染料DiI标记，并直接植入同基因小鼠肝硬化肝脏和正常肝脏的包膜下。在荧光显微镜和共聚焦显微镜下观察肝脏中DiI标记的HCC细胞。对肝硬化肝脏和正常肝脏的组织学分析显示，植入的HCC细胞迁移并侵入相邻的门静脉周围区域，但不侵入相邻的中央小叶区域。HCC的这种特征性行为在肝硬化肝脏中比在正常肝脏中更明显。此外，在植入后7天，在肝硬化肝脏中就观察到未植入肝叶的肝内转移，而在正常肝脏中即使4周后也未检测到。因此，本文描述的伴有肝硬化的HCC原位动物模型可能适合于研究HCC的侵袭和转移行为。重要的是，在原位植入前用荧光染料标记肿瘤细胞可能是一种方便且有用的方法，用于研究各种类型癌症的侵袭和转移行为。
