Inhibition of hepatic metastasis of colon carcinoma by asialo GM₁–positive cells in the liver

Abstract

This study investigates the role of hepatic asialo GM₁–positive cells in inhibiting hepatic metastasis of colon carcinoma (colon adenocarcinoma 38) in mice after administration of a biological response modifier, streptococcal derivative (OK432). Administration of OK432 increased the number of asialo GM₁–positive cells in the liver, enhanced natural killer activity of hepatic mononuclear cells and reduced the number of hepatic metastases of colon carcinoma inoculated into the superior mesenteric vein. Administration of antiserum against asialo GM₁ reduced the number of hepatic asialo GM₁–positive cells, abolished natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases. In addition, administration of antiserum against asialo GM₁ even after OK432 treatment also decreased the number of asialo GM₁–positive cells, reduced natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases of colon carcinoma. However, administration of gadolinium chloride, which suppresses phagocytic function of Kupffer cells, did not influence the natural killer activity of hepatic mononuclear cells or the number of hepatic metastases. In vivo tumor-neutralization assay revealed that tumor growth was inhibited by the hepatic mononuclear asialo GM₁–positive cells, but not by T lymphocytes or Kupffer cells after OK432 administration. These results suggest that an increased number of hepatic asialo GM₁–positive cells after administration of OK432 plays an important role in protecting against metastasis of colon carcinoma in the liver. (HEPATOLOGY 1992;16:469–478.)