Blocking α2 integrins on rat CC531s colon carcinoma cells prevents operation-induced augmentation of liver metastases outgrowth

Authors

  • Gerben J. van der Bij,

    1. Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    2. Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
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  • Steven J. Oosterling,

    1. Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands
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  • Marijn Bögels,

    1. Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
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  • Farien Bhoelan,

    1. Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
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  • Donna M. Fluitsma,

    1. Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
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  • Robert H. J. Beelen,

    1. Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
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  • Sybren Meijer,

    1. Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands
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  • Marjolein van Egmond

    Corresponding author
    1. Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    2. Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
    • Department of Molecular Cell Biology and Immunology, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
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    • fax: (31)-20-4448081


  • Potential conflict of interest: Nothing to report.

Abstract

Currently, an operation is the only curative option for patients with colorectal cancer. Unfortunately, many patients will develop liver metastases even after successful resection of the primary tumor. Removal of primary colorectal carcinoma may paradoxically increase the risk of metastases development, because accumulating evidence suggests that surgical trauma can stimulate tumor growth. In the present study, we investigated the effects of abdominal trauma on liver metastases development. Surgical trauma dramatically increased adhesion of tumor cells in the liver, leading to enhanced outgrowth of metastases. Endothelial stress was observed rapidly after an operation, suggesting that abdominal trauma resulted in impairment of blood vessel integrity. Tumor cells preferentially adhered to extracellular matrix (ECM). Furthermore, preincubation of tumor cells with anti-α2 integrin antibodies completely reverted operation-induced augmentation of CC531s adhesion and liver metastases outgrowth. As such, we postulate that blood vessel integrity in the liver is compromised after abdominal trauma, resulting in enhanced ECM exposure, which enables tumor cell adhesion and metastases outgrowth. Conclusion: Perioperative treatments that either aim to reduce endothelial stress or block the interaction between tumor cells and ECM represent promising new therapeutic strategies for the prevention of liver metastases development after resection of the primary tumor. (HEPATOLOGY 2007.)

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