Abrogation of hematogenous metastases in a murine model by natural killer cells

Abstract

Natural killer (NK) cells are hypothesized to provide resistance against tumors in vivo. The NK system was examined in vivo by the hematogenous dissemination of a murine melanoma in normal C57BL/6 mice (control, athymic homozygous Balb-C nude mice (with increased NK cells), and C57BL/6 beige mice (with decreased NK cells). The highly metastatic F10 subline of the B16 melanoma was maintained in tissue culture to assure high NK sensitivity of the cells. Aliquots of B16-F10 cells in NaCl were injected into the tail vein of 6- to 8-week-old normal mice, nude mice, and beige mice. The mice were killed at 2 weeks and pulmonary nodules were counted under the dissecting microscope. Nude mice were highly resistant to metastases, even at overwhelming doses. Beige mice, however, developed significantly increased numbers of metastases at low doses as compared with control mice (p less than 0.001). We conclude that NK cells serve an important function in the control of tumor metastasis in this in vivo animal preparation. Further investigation of modulation of the NK system in this preparation may elucidate benefits for the treatment of cancer in man.