AsGM1+ NK cells prevent metastasis of invading LD-MCA-38 tumor cells in the nude mouse.
BACKGROUND
Although the liver is a potent tumor cell killing organ it is frequently the site of lethal metastases often signifying the endstage for patients with colorectal cancers. Enhancing hepatic-associated immunity remains elusive until the interactions among hepatic nonparenchymal cells (NPC) are deciphered. We sought to modulate the cellular components of the hepatic immune system of mice with anti-NK and anti-T-cell-neutralizing antibodies in order to determine the cell type most efficacious in preventing liver metastasis.


METHODS
Liver-derived murine colon adenocarcinoma (LD-MCA-38) cells were injected into the ileocolic vein (ICV) of immunocompetent and immunodeficient C57BL/6 mice. Mice were pretreated 1 day prior to tumor cell injection with one of three antibodies: anti-AsGM1, Anti-NK1.1, or Anti-Thy1.2. On Day 21 laparotomy was performed to determine the extent of hepatic tumor foci. The number of hepatic tumor foci was recorded and compared by the Wilcoxon rank sum test.


RESULTS
Mice pretreated with anti-AsGM1 or Anti-NK1.1 developed a massive increase in the number of hepatic tumor foci and decreased survival compared to the control treated mice. Pretreatment with anti-Thy1.2 antibody resulted in a significant decrease in the number of hepatic tumor foci. LD-MCA-38 tumor cells were unable to colonize the liver of C57BL/6 athymic nude mice; however, anti-AsGM1 antibody abolished this antimetastatic effect. There was no difference in the extent of hepatic metastasis and survival between immunodeficient C57BL/6 bg/bg and their conventional littermates bg/+.


CONCLUSIONS
AsGM1+ NK cells exhibit a significant antitumor response in the absence of T-cells. The concept of stimulating NK cell activity and suppressing T-cell function may enhance liver-associated immunity and serve as a deterrent for blood-borne tumor cells metastasizing to the liver.
Volpe
C M
CM
Department of Surgery, Buffalo VA Medical Center and CGF Health Systems, Buffalo, New York, 14203, USA. cmvol@aol.com
Mehta
N
N
Kim
U
U
Hordines
J
J
Doerr
R J
RJ
Cohen
S A
SA
D000230:Adenocarcinoma / Q000517:prevention & control* / Q000556:secondary; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000276:immunology; D000950:Antigens, Ly; D000954:Antigens, Surface; D003110:Colonic Neoplasms / Q000473:pathology*; D005677:G(M1) Ganglioside / Q000276:immunology / Q000378:metabolism*; D007121:Immunocompetence / Q000502:physiology; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology*; D037181:Lectins, C-Type; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000556:secondary; D018655:Lymphocyte Count / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL / Q000235:genetics; D008819:Mice, Nude / Q000276:immunology; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009368:Neoplasm Transplantation; D011506:Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000473:pathology; D018800:Thy-1 Antigens / Q000276:immunology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D018800:Thy-1 Antigens; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside