Analysis of intrahepatic invasion of hepatocellular carcinoma using fluorescent dye-labeled cells in mice

Despite intensive efforts in the treatment of hepatocellular carcinoma (HCC ), its prognosis remains poor, mainly because of intrahepatic metastasis. I t is, therefore, important to investigate the invasive and metastatic behav ior of HCC To examine this, murine HCC cells were labeled with the fluoresc ent carbocyanine dye, DiI and implanted under the capsule of the liver of s yngeneic mice. Optimal conditions are described for labeling HCC cells with DiI. Histological analysis using fluorescent and confocal microscopes reve aled that HCC cells migrate to and invade the adjacent portal vein, but not the adjacent central vein. Conversely, DiI-labeled hepatocytes were shown not to migrate in the liver. These results suggest that intrahepatic metast asis of HCC occurs by invading the portal venous system. Furthermore, it is indicated that orthotopic implantation of fluorescent dye-labeled tumor ce lls may be a convenient and useful method to investigate the invasive and m etastatic behavior of various types of cancer.