BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Regeneration after major hepatectomy accelerates extrahepatic tumor cell engraftment, most probably by acceleration of neovascularization and induction of tumor cell migration.
BACKGROUND: 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. METHODS: 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. RESULTS: After both minor and major hepatectomy tumorproliferating 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. CONCLUSION: Regeneration after major hepatectomy accelerates extrahepatic tumor cell engraftment, most probably by acceleration of neovascularization and induction of tumor cell migration.
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