ANALYSIS OF METASTATIC SPREAD AND GROWTH OF TUMOR-CELLS IN MICE WITH DEPRESSED NATURAL-KILLER ACTIVITY BY ANTI-ASIALO GM1 ANTIBODY OR ANTICANCER AGENTS

The mechanism of artificial and spontaneous metastases of tumor was analyzed in B16 melanoma cells and C57BL/6 mice. Single administrations of 500 .mu.g anti-asialo GM1 antibody resulted in significantly decreased NK activity in spleen cells of C57BL/6 mice. Treatment with anti-asialo GM1 antibody never decreased the function of T lymphocytes. The tumoricidal functions of activated macrophages but not of resident macrophages were decreased treatment with anti-asialo GM1 antibody. Treatment with anti-asialo GM1 antibody 1 day before or on the day of tumor inoculation resulted in a substantial increase in the number of artificial pulmonary metastases. Anti-asialo GM1 antibody most effectively increased the number of pulmonary metastases when administered 1-2 wk before the removal of primary tumor, when the tumor cells are thought to be released into blood circulation from the primary site. Accelerated growth of transplanted tumors at the primary site was observed in mice treated with anti-asialo GM1 antibody. Apparently, anti-asialo GM1 antibody enhances the incidence of metastases and the growth of transplanted tumor mainly by suppressing the function of NK cells. The maximum effective dose (MED) of mitomycin C or its derivative (M-83) suppressed NK activity significantly, and pretreatment with these anticancer agents enhanced the growth of the artificial pulmonary and liver metastases. The MED of cDDP [cis-dichlorodiammine platinum] showed no effect on the NK activity or the numbers of metastases. The depression of NK activity induced by chemotherapy results in the promotion of metastatic disease. NK cells have a key role in the control of metastases of malignant disease, support of NK activity is very important for the prevention of metastases.