ENHANCED TUMOR-GROWTH IN THE RAT-LIVER AFTER SELECTIVE ELIMINATION OFKUPFFER CELLS

The evidence that Kupffer cells are capable of controlling metastatic growth in the liver in vivo is largely circumstantial. The best approa ch when studying natural cytotoxicity activities of Kupffer cells is t o investigate the effect of Kupffer cell elimination on tumour growth. Until now it has not been possible to eliminate Kupffer cells without affecting other cell populations. We have recently developed a new me thod to eliminate Kupffer cells selectively: intravenous injection of liposome-encapsulated (dichloromethylene)bisphosphonate (Cl2MDP-liposo mes) leads to effective elimination of all Kupffer cells, without affe cting non-phagocytic cells. Wag/Rij rats were injected with Cl2MDP-lip osomes. After 48 h, rats were inoculated with syngeneic CC531 colon ca rcinoma cells by injection in the portal system. The results show a st rongly enhanced tumour growth in the liver of the Cl2MDP-liposome-trea ted rats. In these animals, livers were almost completely replaced by tumour and had increased in weight, whereas in the control groups only a few (four to eight) small (1-mm) tumour nodules were found. These d ata show that selective elimination of Kupffer cells results in enhanc ed tumour growth in the liver, implying that Kupffer cells play a cruc ial role in controlling tumour growth in the liver.