Role of Asialo-GjviiPositive Liver Cells from Athymic Nude or Polyinosinic- Polycytidylic Acid-treated Mice in Suppressing Colon-derived Experimental Hepatic Metastasis1

Liver-derived (LD) murine colon adenocarcinoma MCA-38 cells in jected into the ileocolic vein (ICV) of C57BL/6 mice developed distinct hepatic foci within 14-21 days and survived for an average of 19-35 days. In contrast, C57BL/6-nu/ni/ mice given injections of LD-MCA cells by the same route did not develop hepatic lesions. Furthermore, '"Inlabeled LD-MCA-38 tumor cells were rapidly taken up by the liver of conventional mice within l h and 73% of the radioactivity remained after 24 h. However, about 60% of the '"In-labeled LD-MCA-38 tumor cells were cleared from the liver of nude mice after 24 h. Nonparenchymal liver cells isolated from untreated conventional mice displayed little cytotoxicity against freshly excised "Cr-labeled LD-MCA-38 cells but did lyse the standard natural killer target, YAC-1 tumor cells, in 4 h chromium release assays. On the other hand, nonparenchymal liver cells but not spleen cells from nude mice were cytotoxic to "Cr-labeled LDMCA-38 in vitro. The nonparenchymal liver cell population responsible for tumor killing was phenotypically nonadherent and asialo-GMi (AsGMi) positive. C57BL/6 mice treated with polyinosinic-polycytidylic acid |poly(IC)| also displayed cytotoxic activity against LD-MCA-38 tumor cells in vitro. Furthermore, poly(IC) treatment of mice 1-8 days after tumor inoculation suppressed the number of hepatic foci and also signif icantly increased the life span of tumor-bearing mice. Treatment of athymic nude mice or poly(IC)-treated conventional mice with anti-AsGM, induced significant numbers of foci and significantly decreased the life span of MCA-38-bearing mice suggesting that AsG.Mi-positive cells in the liver of these mice may inhibit tumor growth in vivo. In conclusion, the host defense system of the liver from athymic nude or poly(IC)treated mice possess AsGMi-positive cells that can suppress tumor im plantation or tumor growth in the early stages of metastasis in liver.