Induction of E-selectin after partial hepatectomy promotes metastases to liver in mice

Background. The liver is the most frequent site of tumor metastasis. It has been suggested that partial hepatectomy promotes liver metastasis of malig nant disease and that expression of E-selectin, a cell adhesion molecule, p lays roles in tumor metastasis. However, no reports are available concernin g the expression of E-selectin after hepatectomy. Methods. In the present study, we used BALB/c mice subjected to 30% partial hepatectomy after injection of 1 x 10(4) colon 26 cells to determine the e ffects of partial hepatectomy on tumor metastasis to liver. E-Selectin expr ession within the liver after partial hepatectomy was evaluated using rever se transcription polymerase chain reaction and Western blotting. In additio n, we injected polyclonal antibody to E-selectin into mice in which partial hepatectomy had augmented liver metastasis. Results. Mice subjected to partial hepatectomy had significantly increased numbers of liver metastases (sham operation, 1.5 +/- 2.0, vs partial hepate ctomy, 35.5 +/- 19.3; P < 0.001). Expression of E-selectin mRNA within the liver was markedly increased 4 h after partial hepatectomy, but subsequentl y decreased at 24 h. E-Selectin protein was detected 8 h after hepatectomy, but subsequently decreased at 24 h as measured by Western blotting. Mice s ubjected to intraperitoneal injection of neutralizing antibody after operat ion had significantly decreased numbers of liver metastases (phosphate-buff ered saline, 20.6 +/- 9.2, P < 0.05, and normal IgG, 18.0 +/- 8.0, P < 0.05 , compared with polyclonal antibody to E-selectin, 5.6 +/- 4.8). Conclusion. Induction of E-selectin by partial hepatectomy promotes hematog enous liver metastasis. Our findings can be applied to surgical treatment o f liver tumor to reduce the recurrence of liver metastasis after hepatectom y by inhibiting E-selectin-mediated adhesion using reagents to E-selectin. (C) 2001 Academic Press.