Obstructive jaundice facilitates hepatic metastasis of B16F1 mouse melanoma cells: participation of increased VCAM-1 expression in the liver

Obstructive jaundice facilitates experimental liver metastasis in the rat m odel, but the detailed mechanisms of this facilitation remain unclear. This study aimed to evaluate the contribution of vascular cell adhesive molecul es-1 (VCAM-1) to augmented hepatic metastasis in cases of obstructive jaund ice. Obstructive jaundice was induced in male C57BL/6 mice by common bile d uct obstruction for 5 days using a Surgiclip. For the biliary decompression , obstructive jaundice was induced for 5 days, followed by removal of the S urgiclip. Liver specimens and blood samples were obtained from animals 5 da ys after biliary obstruction (OJ5) or sham operation and 2, 5, 11, 14 days after biliary decompression. The expression of VCAM-1 mRNA was increased in the livers from the OJ5 group. Western blot analysis demonstrated increase d expression of VCAM-1 protein in the livers of the OJ5 group, in contrast with low VCAM-1 expression in the sham group. The expression of VCAM-1 prot ein was sustained at high levels at 2 days and decreased at 5 days after bi liary decompression (BD5). For the induction of experimental hepatic metast asis, male C57BL/6 mice were randomized to three groups (sham, OJ5, BD5) of six animals each. B16F1 melanoma cells were introduced into the animals by an intraportal injection. Metastatic colonies in the livers were investiga ted 13 days after inoculation. The mean number of metastatic colonies was s ignificantly increased in the OJ5 group (70.5 +/- 51.2) compared to that of the sham group (7.2 +/- 7.9) (p < 0.05). This augmentation of hepatic meta stasis was abrogated in the BD5 group (16.8 <plus/minus> 20.3). In conclusi on, our results suggest that augmented hepatic metastasis in cases of obstr uctive jaundice are partly mediated through VCAM-1/VLA-4 interaction.