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The microscopic anatomy of experimental rat CC531 colon tumour metastases: Consequences for immunotherapy?

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Abstract

The colon adenocarcinoma cell line CC531 was adopted as a model for immunotherapeutical treatment of experimental colorectal metastases in a syngeneic rat model. We studied the presence and localization of T and natural killer cells, vessels and matrix proteins in in vivo growing CC531 tumours by immunohistochemistry. CC531 tumours were induced either in the lungs by injecting CC531 tumour cells into a tail vein or in the liver by injection of CC531 tumour cells under the liver capsule or into a mesenteric vein. All 3 tumour types were composed of islets of tightly apposed tumour cells surrounded by abundantly present tumour-stroma which contained tumour vessels and matrix proteins. Some of these matrix proteins, especially laminin and collagen IV formed a basal membrane-like structure around the tumour nodules. This structure was most pronounced in mesenteric vein-induced liver tumours and less prominent in subcapsular-induced liver tumours and tail vein-induced lung tumours. Tumour-infiltrating lymphocytes of both T and natural killer cell origin were found in the tumours, but predominantly in the tumour stroma, separated from the islets of tumour cells by the basal membrane-like structure. We hypothesize that the matrix proteins of these tumours play an ambivalent role: they may provide a substratum for migration of effector cells into the tumour stroma but may also provide a barrier preventing direct contact between tumour target cells and immune effector cells.

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Authors and Affiliations

  1. Departments of Surgery and Pathology, Leiden University Medical Center, Leiden, The Netherlands

    Martin Hagenaars

  2. Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

    N. Geeske Ensink, Cornelis J.H. van de Velde & Peter J.K. Kuppen

  3. University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA

    Per H. Basse

  4. Department of Medical Microbiology & Immunology, University of Århus, Denmark

    M. Hokland

  5. Department of Anatomy and Cell Biology, University of Göteborg, Sweden

    U. Nannmark

  6. Department of Surgery, University Hospital Rotterdam-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

    Alexander M.M. Eggermont

  7. Pathology, Leiden University Medical Center, Leiden, The Netherlands

    Gert Jan Fleuren

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  1. Martin Hagenaars
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  2. N. Geeske Ensink
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  6. Alexander M.M. Eggermont
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  9. Peter J.K. Kuppen
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Hagenaars, M., Ensink, N.G., Basse, P.H. et al. The microscopic anatomy of experimental rat CC531 colon tumour metastases: Consequences for immunotherapy?. Clin Exp Metastasis 18, 189–196 (2000). https://doi.org/10.1023/A:1006774602360

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  • DOI: https://doi.org/10.1023/A:1006774602360

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