ROLE OF KUPFFER CELLS IN ARRESTING CIRCULATING TUMOR-CELLS AND CONTROLLING METASTATIC GROWTH IN THE LIVER

Metastasis to the liver is a common event in clinical oncology, Blood- borne tumor cells (TCs) arriving 60 the liver sinusoids run into a spe cial vascular bed, The lining of liver sinusoids is shared by Kupffer cells (KCs) and endothelial cells. KCs, liver-fixed macrophages, are r esponsible for defection and removal of ''non-self'' particles. To inv estigate their role in arresting blood-borne TCs and controlling tumor growth, we injected a syngeneic colon carcinoma cell line into a mese nteric vein of two groups of rats; one group was without Kupffer cells and the other normal controls. We removed the Liver of these animals at different time intervals and performed immunohistochemical analysis with monoclonal antibodies (MoAbs) against our tumor cell line, three macrophage subpopulations, natural killer cells, and B and T lymphocy tes. Additionally, we showed in vitro spontaneous cytotoxicity of KCs against our tumor cell line. Results suggest that KCs play a relevant role in arresting circulating TCs at the liver sinusoid, although it i s limited to a small number of malignant cells. They also seem to play a major role in clearing neoplastic cells from the fiver parenchyma, in controlling tumor growth in the very early stages of metastatic dev elopment, and in modulating the host immune response to cancer cells.