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

Rat hepatoma tissue culture cells have retained only a few liver-specific membrane functions. To find out whether trans formation of these cells led to the appearance of tumor-specific membrane glycoprotein structures, which might also be pres ent in released form in the circulation of tumor-bearing animals, we compared ¡mmunologically the sera and ascites fluids of normal and of hepatoma-bearing rats. For structural identifi cation, 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 mem branes 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. Char acterization 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 glycopro teins. The result was the accumulation of the acidic forms of the antigen in the serum and ascites fluid of tumor-bearing