Portal vein ligation and partial hepatectomy differentially influence growth of intrahepatic metastasis and liver regeneration in mice.

Abstract

BACKGROUND/AIMS: Since modern treatment of liver metastases includes serial hepatectomies and portal vein obstruction, we investigated the effects of portal vein ligation (PVL) and partial hepatectomy (PH) on tumor growth. METHODS: The effects of 70% PH and PVL on liver and lung metastases were evaluated in mice. Tumor growth and liver regeneration were assessed by morphometry and immunohistochemistry for PCNA and BrdU. The effect of growth factors of liver regeneration on CT-26 cells was tested in vitro, and TGF-beta secretion of CT-26 cells was measured by ELISA. RNA synthesis of TGF-beta and activin A was measured by RT-PCR. RESULTS: Liver regeneration after PH and PVL was similar in tumor-free mice. Intrahepatic tumor growth was lower after PH than after PVL (p=0.016). Extrahepatic tumor growth was not different. In contrast to PVL, liver regeneration was delayed after PH in metastatic livers (p=0.001). Tested growth factors of liver regeneration stimulated CT-26 cells in vitro, and CT-26 secreted significant amounts of TGF-beta in vitro and in vivo. CONCLUSIONS: Although similar in tumor-free mice, liver regeneration significantly differed between PVL and PH in metastatic livers. In addition, PH and PVL differently affected intrahepatic tumor growth.