Inhibition of experimental hepatic metastasis by a monoclonal antibody that blocks tumor-hepatocyte interaction.
The role of tumor-hepatocyte interaction in carcinoma metastasis to the liver was investigated with use of the liver-metastatic murine carcinoma H-59 and a monoclonal antibody (MAb) C-11, which can inhibit tumor cell adhesion to hepatocytes in vitro by blocking a 64-71-kD glycoprotein receptor expressed on the tumor cell surface. The effect of this antibody on liver colonization by H-59 cells was analyzed. We found that treatment of H-59 cells with the antibody or with F(ab)2 fragments prior to tumor cell inoculation markedly and specifically reduced the ability of the cells to form hepatic metastases. An inhibitory effect was also seen when the antibodies were administered directly to tumor-inoculated mice. In contrast, no reduction was seen in the number of lung metastases when the antibody-treated cells were inoculated intravenously. Studies in vitro revealed that coculture of the tumor cells with hepatocytes had a stimulatory effect on tumor cell proliferation that could be specifically blocked by MAb C-11. The results suggest that H-59 cell adhesion to hepatocytes via the plasma membrane receptor promotes liver metastases formation and provide further evidence that biological reagents that can abrogate specific tumor-host cell interactions may be beneficial in the prevention of tumor cell dissemination.
Wang
J
J
Department of Surgery, McGill University, Montreal, Quebec, Canada.
Fallavollita
L
L
Brodt
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D005260:Female; D007167:Immunotherapy; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000503:physiopathology / Q000556:secondary; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal