The binding of epidermal growth factor, asialoorosomucoid, and apoprotein E-rich lipoproteins to isolated hepatocytes was investigated at various time intervals during the step-by-step development of liver cancer in rats. The degree of binding of the three ligands showed a progressive reduction in early persistent and late persistent putative preneoplastic hepatocyte nodules. This was further decreased in hepatocytes isolated from unequivocal hepatocellular carcinomas. Regenerating liver hepatocytes bound lesser amounts of epidermal growth factor and asialoorosomucoid than did hepatocytes from control resting liver but increased amounts of apoprotein E-rich lipoproteins. The progressive decrease in ligand binding during the precancerous phase of hepatocarcinogenesis, the nodule-to-cancer sequence, may render nodules less responsive to the influences of their external environments.
This research was supported by grants from the National Cancer Institute of Canada, the Medical Research Council of Canada (MT 5994), and the USPHS (CA 21157) from the National Cancer Institute, Department of Health and Human Services.