In vivo activation of NK cells induces inhibition of lung colonization of H-2 positive and H-2 negative fibrosarcoma tumor clones.
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.
Algarra
I
I
Department of Clinical Analysis and Immunology, Universidad de Granada, Spain.
Pérez
M
M
Gaforio
J J
JJ
Gasca
F
F
Garrido
F
F
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005677:G(M1) Ganglioside / Q000276:immunology; D006183:H-2 Antigens / Q000032:analysis*; D007106:Immune Sera / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000556:secondary*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D013994:Tilorone / Q000627:therapeutic use*
D006183:H-2 Antigens; D007106:Immune Sera; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D013994:Tilorone