In vivo activation of NK cells induces inhibition of lung colonization of H-2 positive and H-2 negative fibrosarcoma tumor clones

• Published in: Clinical & experimental metastasis 1994-01, Vol.12 (1), p.31-36
• Main Authors: Algarra, I, Pérez, M, Gaforio, J J, Gasca, F, Garrido, F
• Format: Article
• Language: English
• Subjects: Animals; Cytotoxicity, Immunologic; Fibrosarcoma - drug therapy; Fibrosarcoma - immunology; Fibrosarcoma - pathology; G(M1) Ganglioside - immunology; H-2 Antigens - analysis; Immune Sera - immunology; Killer Cells, Natural - immunology; Lung Neoplasms - secondary; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Tilorone - therapeutic use
• ISSN: 0262-0898; 1573-7276
• DOI: 10.1007/BF01784331

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.