Role of asialo-GM1 positive liver cells from athymic nude or polyinosinic-polycytidylic acid-treated mice in suppressing colon-derived experimental hepatic metastasis.
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.
Cohen
S A
SA
Department of Medicine, VA Medical Center, Buffalo, New York 14215.
Tzung
S P
SP
Doerr
R J
RJ
Goldrosen
M H
MH
D000230:Adenocarcinoma / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D004261:DNA Replication / Q000187:drug effects*; D005732:Gangliosides; D006028:Glycosphingolipids / Q000276:immunology / Q000502:physiology*; D007106:Immune Sera; D008099:Liver / Q000503:physiopathology*; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011070:Poly I-C / Q000627:therapeutic use*
D005732:Gangliosides; D006028:Glycosphingolipids; D007106:Immune Sera; C038244:ganglio-N-triaosylceramide; D011070:Poly I-C