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The Influence of Liver Resection on Intrahepatic Tumor Growth
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Surgery-induced reactive oxygen species enhance colon carcinoma cell binding by disrupting the liver endothelial cell

Nuray Gül1, Marijn Bögels, Simran Grewal

  • 1Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. n.gul@vumc.nl

Gut
|February 1, 2011
PubMed
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Surgery triggers reactive oxygen species (ROS) that damage the liver lining, increasing colorectal cancer metastasis risk. ROS scavengers and Kupffer cell modulation may reduce this risk.

Area of Science:

  • Oncology
  • Immunology
  • Vascular Biology

Background:

  • Colorectal cancer surgery increases liver metastasis risk.
  • Surgery induces an inflammatory response, promoting tumor cell adhesion in the liver.
  • Reactive oxygen species (ROS) are implicated in this surgery-induced inflammatory process.

Purpose of the Study:

  • To investigate the effects of ROS on liver vascular integrity.
  • To determine the role of ROS in surgery-induced tumor cell adhesion to the liver.
  • To explore the involvement of Kupffer cells in this process.

Main Methods:

  • Assessed endothelial cell monolayers (HUVECs, HMEC-1s) exposed to ROS.
  • Measured electrical impedance, cellular integrity, and tumor cell adhesion.

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  • Studied surgery-induced tumor cell adhesion, ROS, and Kupffer cells in vivo in rats.

    • Main Results:

    • ROS decreased endothelial cell impedance and integrity, forming gaps that allowed tumor cell adhesion.
    • Surgery downregulated liver tight junction proteins; ROS scavengers and Kupffer cell depletion prevented this.
    • Edaravone (ROS scavenger) and Kupffer cell depletion reduced surgery-induced tumor cell adhesion in rats.

    Conclusions:

    • Surgery-induced ROS, produced by macrophages, damages the liver vascular lining by downregulating tight junction proteins.
    • This damage exposes the extracellular matrix, facilitating circulating tumor cell binding and liver metastasis.
    • Perioperative interventions targeting inflammation may reduce liver metastasis and improve outcomes for colorectal cancer patients.