ganglio-n-triaosylceramide and Adenocarcinoma

Liver-derived (LD) murine colon adenocarcinoma MCA-38 cells injected 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/nu mice given injections of LD-MCA cells by the same route did not develop hepatic lesions. Furthermore, 111In-labeled LD-MCA-38 tumor cells were rapidly taken up by the liver of conventional mice within 1 h and 73% of the radioactivity remained after 24 h. However, about 60% of the 111In-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 51Cr-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 51CR-labeled LD-MCA-38 in vitro. The nonparenchymal liver cell population responsible for tumor killing was phenotypically nonadherent and asialo-GM1 (AsGM1) 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 significantly increased the life span of tumor-bearing mice. Treatment of athymic nude mice or poly(IC)-treated conventional mice with anti-AsGM1 induced significant numbers of foci and significantly decreased the life span of MCA-38-bearing mice suggesting that AsGM1-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 AsGM1-positive cells that can suppress tumor implantation or tumor growth in the early stages of metastasis in liver.

Topics: Adenocarcinoma; Animals; Colonic Neoplasms; DNA Replication; Gangliosides; Glycosphingolipids; Immune Sera; Liver; Liver Neoplasms; Male; Mice; Mice, Inbred C57BL; Mice, Nude; Poly I-C