INHIBITION OF EXPERIMENTAL HEPATIC METASTASIS BY A MONOCLONAL-ANTIBODY THAT BLOCKS TUMOR-HEPATOCYTE INTERACTION

The role of tumor-hepatocyte interaction in carcinoma metastasis to th e liver was investigated with use of the liver-metastatic murine carci noma H-59 and a monoclonal antibody (MAb) C-11, which can inhibit tumo r cell adhesion to hepatocytes in vitro by blocking a 64-71-kD glycopr otein receptor expressed on the tumor cell surface. The effect of this antibody on liver colonization by H-59 cells was analyzed. We found t hat treatment of H-59 cell's with the antibody or with F(ab)(2) fragme nts prior to tumor cell inoculation markedly and specifically reduced the ability of the cells to form hepatic metastases. An inhibitory eff ect was also seen when the antibodies were administered directly to tu mor-inoculated mice. In contrast, no reduction was seen in the number of lung metastases when the antibody-treated cells were inoculated int ravenously. Studies in vitro revealed that coculture of the tumor cell s with hepatocytes had a stimulatory effect on tumor cell proliferatio n that could be specifically blocked by MAb C-11. The results suggest that H-59 cell adhesion to hepatocytes via the plasma membrane recepto r promotes liver metastases formation and provide further evidence tha t biological reagents that can abrogate specific tumor-host cell inter actions may be beneficial in the prevention of tumor cell disseminatio n.