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

Authors: Hagenaars, Martin¹; Ensink, N.²; Basse, Per³; Hokland, M.⁴; Nannmark, U.⁵; Eggermont, Alexander⁶; van de Velde, Cornelis²; Fleuren, Gert⁷; Kuppen, Peter²

Source: Clinical and Experimental Metastasis, Volume 18, Number 2, March 2000 , pp. 189-196(8)

Publisher: Springer

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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.

Keywords: colon cancer; immunotherapy; matrix proteins; metastasis; rat

Document Type: Research article

DOI: 10.1023/A:1006774602360

Affiliations: 1: Departments of Surgery and Pathology, 011011011011011011011011Leiden University Medical Center, Leiden, 011011011011011011011011011The Netherlands, 2: Department of Surgery, 011011011011011011011011Leiden University Medical Center, Leiden, 011011011011011011011011011The Netherlands, 3: University of Pittsburgh Cancer Institute, Pittsburgh, 011011011011011011011011011Pennsylvania, 011011011011011011011011011USA, 4: Department of Medical Microbiology & Immunology, 011011011011011011011011University of Århus, Denmark, 5: Department of Anatomy and Cell Biology, 011011011011011011011011University of Göteborg, Sweden, 6: Department of Surgery, 011011011011011011011011University Hospital Rotterdam-Daniel den Hoed Cancer Center, Rotterdam, 011011011011011011011011011The Netherlands, 7: Pathology, 011011011011011011011011Leiden University Medical Center, Leiden, 011011011011011011011011011The Netherlands,

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