Liver metastasis model of colon cancer in the rat: immunohistochemical characterization

Abstract

Inoculation of 3 x 10(4) to 3 x 10(5) CC531 colon adenocarcinoma cells into the portal vein of syngeneic WAG/Rij rats provides a reproducible animal model of colon cancer liver metastasis with macroscopically visible tumor nodules at day 25 after inoculation. In this study, the inflammatory cell response in the liver sinusoids against locally induced metastases was also investigated using immunohistochemical methods. Host immune reactive cells accumulated in the liver sinusoids of tumor-bearing livers, especially resident Kupffer cells (KC; ED1+/ED2+), and to a lesser extent pit cells (OX8+/0X19-), T lymphocytes (OX8+/OX19+) and polymorphonuclear leukocytes (PMN; HIS48+). All these cell types may be involved in the lysis of CC531 cells in the liver, although only major histocompatibility complex class II+ monocytes (3D11+/ED1+/ED2-), but not resident KC, T lymphocytes nor PMN, accumulated at the peritumoral area between liver parenchyma and tumor foci. Especially monocytes but also PMN, lymphocytes and pit cells appeared to infiltrate the stromal tumor compartment. In view of the low cell dose needed, the rat liver metastasis model of colon cancer used in this study reflects well the human, weakly immunogenic, tumor-host relationships and provides an excellent opportunity for the study of cellular reactions related to chemo- and/or immunotherapy protocols.