Early events of hepatic metastasis formation in mice: Role of Kupffer and NK-cells in natural and interferon-gamma-stimulated defense

Surgical manipulation of a tumor may result in increased influx of tumor ce lls into the systemic and portal circulation and give rise to formation of metastases. In addition, major surgery has been reported to cause profound immunosuppression. In an attempt to increase the host-antitumor immune mech anisms following surgery we have studied the effect of preoperative adminis tration of interferon-gamma, related to the antimetastatic effects of Kupff er cells (HC) and natural killer cells (NK-cells) in the early phase of liv er metastasis formation. Colon carcinoma cells were injected into the super ior mesenteric vein of syngeneic mice and after 17 days metastases were qua ntified by weight, number, and uptake of [I-125]iododeoxyuridine. Unstimula ted control mice developed 10.5 surface nodules per liver 17 days following injection of colon carcinoma cells into the superior mesenteric vein of sy ngeneic mice. This figure was only 2.6 in mice stimulated with a single dos e of 1000 IU IFN-gamma, 4 h prior to inoculation of tumor cells. Administra tion of GdCl3, which is reported to deplete and block the function of Kupff er cells, 24 h prior to tumor cell inoculation resulted in a B-fold tumor m ass increase relative to control. Injection of anti-asiolo-GM(1) antiserum, which eliminates the hepatic NK-cells, induced a 10-fold increase in tumor mass. These results indicate an important early antimetastatic function of hepatic NK-cells and KC and that presurgical administration of IFN-gamma m ay be important for eliminating circulating tumor cells and inhibiting deve lopment of residual tumors. (C) 1999 Academic Press.