Visualizing Portal Vein Metastatic Trafficking to the Liver with Green Fluorescent Protein-expressing Tumor Cells

Abstract

Cell migration or trafficking is an integral aspect of cancer metastasis and is a target for development of novel antimetastatic therapy. Tumor cell trafficking has been a poorly understood phenomenon due to the inability to visualize the process. In this study, we visualized the trafficking of metastatic cells targeting the liver via the portal vein using green fluorescent protein (GFP)-expressing cancer cells. Within 72 h after transplantation of tumor cells, on the ascending colon in nude mice, metastasis was visualized ex vivo on a single-cell basis around the portal vein by GFP imaging. At this early time-point, a few cells were visualized trafficking to the liver via the portal vein. By post-implantation day-5, the caudate lobe of the liver was involved with trafficking metastatic cells. Metastasis around the portal vein increased more rapidly than those in other areas of the liver. By day-7 post-implantation, the right lateral lobe of the liver was involved with trafficking metastatic cells. By days-9 and -11, metastasis increased rapidly around the portal vein and then spread to other areas of the liver. These experiments demonstrate the critical role of the portal vein in metastasis to the liver.