Regular Article
Hepatic Ischemia–Reperfusion Promotes Liver Metastasis of Colon Cancer

https://doi.org/10.1006/jsre.2002.6356Get rights and content

Abstract

Background. The effects of hepatic ischemia/reperfusion (I/R) on liver metastasis have not been fully examined. We examined hepatic I/R and liver metastasis of colorectal cancer in a rat model; we also quantitated expression of E-selectin (ELAM-1) mRNA after I/R.

Materials and methods. Rats underwent 30 or 60 min of 70% partial hepatic ischemia. After 60 min of reperfusion, rat colon adenocarcinoma cells (RCN-H4) were inoculated intrasplenically. The number of tumor nodules on the liver surface was determined 3 weeks later. Expression of E-selectin mRNA was determined at 1, 3, and 6 h after ischemia by quantitative RT–PCR.

Results. Hepatic I/R promoted liver metastasis of RCN-H4 and induced the expression of E-selectin mRNA in both clamped and unclamped liver lobes. The number of tumor nodules and the expression of E-selectin mRNA after 60 min of ischemia was greater than that after 30 min.

Conclusions. Hepatic I/R, especially with a long duration of ischemia, induces expression of E-selectin and promotes liver metastasis of colon cancer in rats.

References (40)

  • L.M. Colletti et al.

    The role of cytokine networks in the local liver injury following hepatic ischemia/reperfusion in the rat

    Hepatology

    (1996)
  • A. Higashiyama et al.

    Involvement of tumor necrosis factor alpha and very late activation antigen 4/vascular cell adhesion molecule 1 interaction in surgical-stress-enhanced experimental metastasis

    Cancer Immunol. Immunother.

    (1996)
  • M.J. Anasagasti et al.

    Sinusoidal endothelium release of hydrogen peroxide enhances very late antigen-4-mediated melanoma cell adherence and tumor cytotoxicity during interleukin-1 promotion of hepatic melanoma metastasis in mice

    Hepatology

    (1997)
  • F. Vidal-Vanaclocha et al.

    Interleukin 1 (IL-1)-dependent melanoma hepatic metastasis in vivo; increased endothelial adherence by IL-1-induced mannose receptors and growth factor production in vitro

    J. Natl. Cancer Inst.

    (1996)
  • F. Vidal-Vanaclocha et al.

    Interleukin-1 receptor blockade reduces the number and size of murine B16 melanoma hepatic metastases

    Cancer Res.

    (1994)
  • T. Horiuchi et al.

    Optimal cycles of hepatic ischemia and reperfusion for intermittent pedicle clamping during liver surgery

    Arch. Surg.

    (1995)
  • M.P. Bevilacqua et al.

    Endothelial leukocyte adhesion molecule 1: An inducible receptor for neutrophils related to complement regulatory proteins and lectins

    Science

    (1989)
  • M.P. Bevilacqua et al.

    Selectins

    J. Clin. Invest.

    (1993)
  • S. Nakamori et al.

    Increased expression of sialyl Lewisx antigen correlates with poor survival in patients with colorectal carcinoma: Clinicopathological and immunohistochemical study

    Cancer Res.

    (1993)
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    To whom correspondence and reprint requests should be addressed at Second Department of Surgery, Fukui Medical University, 23-3 Shimoaizuki Matsuoka-cho, Yoshida-gun Fukui-ken 910-1193, Japan. Fax: 81-776-61-8114. E-mail: [email protected].

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