The role of different
tilorone analogs in the abrogation of the metastatic spread of H-2 positive and H-2 negative
tumor clones was studied. Pre-treatment of BALB/c mice with RMI 10,874DA compound completely abolished lung colonization of an H-2 negative (GR9.B9) MCA-induced
fibrosarcoma clone in an experimental
metastasis assay. This effect was also evident when clones were treated with other
tilorone analogs (R11,567DA or R11,513DA). Other H-2 positive and H-2 negative chemically induced
fibrosarcoma clones were also tested. The effect was not due to direct toxicity of the
tilorone analog on
tumor cells, but instead was dependent on NK cells; this was suggested by the finding that treatment of mice with anti-
asialo GM1 abrogated the effect of the
tilorone analog (RMI 10,874DA compound). Interestingly, the inhibition of lung colonization after
intravenous injection was again observed regardless of the H-2 phenotype of the
tumor clones, and H-2+ and H-2- clones were similarly inhibited. In vitro assays of NK sensitivity of
tumor clones showed that lysis varied depending on the H-2 phenotype of
tumor clones, indicating an absence of correlation between in vivo and in vitro results.