The Clinical and Physiological Implications of Hepatoma b1₂-binding Proteins¹

A serum B₁₂-binding protein with increased sialic acid content (termed hepatoma B₁₂-binding protein) that causes elevations of serum B₁₂and unsaturated B₁₂-binding capacity has been found in some patients with hepatocellular carcinoma (hepatoma). We now report another patient with hepatoma with initial near-normal, unsaturated B₁₂-binding capacity that increased 400-fold as the disease progressed and then fell 50% with response to chemotherapy. A perfusate of the tumor in the liver had 5 times more B₁₂-binding protein than did the serum and was immunologically the same as the serum hepatoma B₁₂-binding protein isolated from previous cases. A cell line derived from hepatoma produced significant amounts of B₁₂-binding protein similar to hepatoma B₁₂-binding protein, whereas cell lines from normal liver and other neoplasia did not. The hepatoma sera, perfusate, and media from the hepatoma cell line contained elevated sialyltransferase activity. These data suggest that some hepatomas produce increased hypersi-alylated B₁₂-binding protein that is cleared slowly from the plasma and accumulates there as hepatoma B₁₂-binding protein.