Major but not minor hepatectomy accelerates engraftment of extrahepatic tumor cells

Abstract

The effect of hepatectomy and hepatic regeneration on intra- and extrahepatic tumor growth is still controversially discussed. Herein we studied the effect of minor (30%) or major (70%) hepatectomy on engraftment of extrahepatic tumor cells, and the role of tumor neovascularization and tumor cell migration. Green fluorescent protein (GFP)-transfected CT26.WT colorectal cancer cells were implanted in dorsal skinfold chambers of syngeneic BALB/c mice. Animals underwent 30% (30%Phx, n = 8) or 70% hepatectomy (70%Phx, n = 8). Sham-operated animals served as controls (n = 8). Angiogenesis and neovascularization as well as tumor cell migration, proliferation and growth were studied over 14 days using intravital fluorescence microscopy, histology and immunohistochemistry. After both minor and major hepatectomy tumor proliferating cell nuclear antigen (PCNA) expression increased significantly (P < 0.05) when compared with nonhepatectomized controls. However, only major but not minor hepatectomy accelerated neovascularization (P < 0.05) and tumor cell migration (P < 0.05). This was associated with a significantly (P < 0.05) enhanced tumor growth after 70%Phx when compared with 30%Phx and controls. The rate of apoptotic cell death was not affected by major or minor hepatectomy. Regeneration after major hepatectomy accelerates extrahepatic tumor cell engraftment, most probably by acceleration of neovascularization and induction of tumor cell migration.