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Macrophages promote tumour growth and liver metastasis in an orthotopic syngeneic mouse model of colon cancer

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Tumour-associated macrophages have been shown to promote proliferation, angiogenesis and metastasis in several carcinomas. The effect on colon cancer has not yet been clarified. Furthermore, Kupffer cells in the liver might initiate the formation of metastases by directly binding tumour cells.

Methods

An orthotopic syngeneic mouse model of colon cancer as well as a liver metastases model has been studied, using murine CT-26 colon cancer cells in Balb/c-mice. Macrophages were depleted in both models by clodronate liposomes. Tumour sizes and metastases were determined using 7-Tesla MRI. The macrophage and vascular density in the orthotopic tumours as well as the Kupffer cell density in the livers were evaluated using immunohistochemistry.

Results

Animals in the macrophage-depleted group displayed significantly smaller primary tumours (37 ± 20 mm3) compared to the control group (683 ± 389 mm3, p = 0.0072). None of the mice in the depleted group showed liver or peritoneal metastases, whereas four of six control mice displayed liver and five out of six mice peritoneal metastases. The vascular density was significantly lower in the macrophage-depleted group (p = 0.0043). In the liver metastases model, animals of the Kupffer cell-depleted group (14.3 ± 7.7) showed significantly less liver metastases than mice of the two control groups (PBS liposomes, 118.5 ± 28.2, p = 0.0117; NaCl, 81.7 ± 23.2, p = 0.0266). The number of liver metastases correlated directly with the Kupffer cell density (p = 0.0221).

Conclusion

Macrophages promote tumour growth, angiogenesis and metastases in this orthotopic syngeneic mouse model. Kupffer cells enhance the formation of metastases in the liver.

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Acknowledgments

The study was supported by the German Federal Ministry of Education and Research BMBF, grant no. 0314107.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of General, Visceral, Thoracic and Vascular Surgery, University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse, 17475, Greifswald, Germany

    J. Kruse, W. von Bernstorff, N. Albers, S. Hagemann, C. Günther, C.-D. Heidecke, L. I. Partecke & L. I. Partecke

  2. Department of Pathology, University Medicine Greifswald, Friedrich-Loeffler-Strasse 23e, 17487, Greifswald, Germany

    K. Evert

  3. Department of Radiology, University Medicine Greifswald, Ferdinand-Sauerbruch-Strasse, 17475, Greifswald, Germany

    S. Hadlich

  4. Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit, VUMC, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands

    N. van Rooijen

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  1. J. Kruse
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Correspondence to L. I. Partecke.

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Kruse, J., von Bernstorff, W., Evert, K. et al. Macrophages promote tumour growth and liver metastasis in an orthotopic syngeneic mouse model of colon cancer. Int J Colorectal Dis 28, 1337–1349 (2013). https://doi.org/10.1007/s00384-013-1703-z

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  • DOI: https://doi.org/10.1007/s00384-013-1703-z

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