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Influence of the Liver on the Profile of Circulating Antigens Recognized by Antiserum against Hepatoma Membrane Glycoproteins¹

Department of Cell and Tumor Biology, Roswell Park Memorial Institute, Buffalo, New York 14263

Rat hepatoma tissue culture cells have retained only a few liver-specific membrane functions. To find out whether transformation of these cells led to the appearance of tumor-specific membrane glycoprotein structures, which might also be present in released form in the circulation of tumor-bearing animals, we compared immunologically the sera and ascites fluids of normal and of hepatoma-bearing rats. For structural identification, we used polyspecific antibodies against the membrane glycoproteins of the hepatoma cells. Crossed immunoelectrophoresis of the body fluids resulted in the separation of several antigens, one of which appears to be tumor specific. Immunoelectrophoretic analyses of the glycoproteins from the membranes of liver and hepatoma cells revealed many shared antigens; in one instance, we could assign the membrane associated form to major antigen detected in the serum. Characterization of the molecular size and charge of two selected antigens by two-dimensional gel electrophoresis indicated that the hepatoma cell products were not completely sialylated. In the case of the circulating, hepatoma-specific antigen, this property appears to result in hepatic clearance of the more basic ("asialo") portion of the glycoprotein species via the receptor-mediated uptake of galactose-terminated glycoproteins. The result was the accumulation of the acidic forms of the antigen in the serum and ascites fluid of tumor-bearing rats.

¹ This work was supported by Grant CA-26122 from the National Cancer Institute and by Institutional Biomedical Research Support Grant 60020-13.

Received 10/21/81. Accepted 3/10/82.