Lung colonization and metastasis by disseminated B16 melanoma cells: H-2 associated control at the level of the host and the tumor cell.
We have studied the experimental metastasis of H-2+ and H-2- melanoma sublines in H-2b/b and H-2a/b hosts by enumerating pulmonary colonies 20-50 days after i.v. inoculation of tumor cells. In H-2b/b hosts, the H-2+ "B16-S" cells gave rise to a moderate number of metastatic colonies (mean: 6.3 +/- 6). The "BL16-L" sublines that had lost the expression of MHC class-I antigens, according to FACS-analysis and quantitative absorption tests, gave no metastases under the same conditions. Pretreatment of the H-2+ met+ B16-S with interferons (beta or alpha + beta) increased their H-2 antigen expression and the number of metastatic colonies (mean: 25 +/- 16). Interferon pretreatment of B16-L cells partially restored their H-2b expression and induced them to form a small number of metastatic colonies. The reduction in pulmonary colonization by the H-2 negative B16-L cells could be attributed to their rapid elimination by natural killer cells, already observed within 24 hr of inoculation of radiolabelled cells. H-2- B16-L cells were more susceptible than H-2+ B16-S cells to in vitro lysis by poly I:C-treated splenocytes, and they acquired full metastatic abilities if the hosts were treated with anti-asialo GM-I serum. In H-2a/b heterozygous hosts, the H-2+ B16-S cells also failed to metastasize. Reduced pulmonary colonization was evident by 24 hr after injection in comparison with H-2b/b hosts, and could be reversed by anti-asialo GM-I treatment of the hosts. In vitro, H-2a/b splenocytes were more cytotoxic to the B16 cells than syngeneic effectors. The results are discussed in relation to a recent hypothesis on a surveillance mechanism for elimination of cells on the basis of their lack (or insufficient expression) of host MHC genes.
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology*; D006579:Heterozygote; D006720:Homozygote; D007113:Immunity, Innate; D007370:Interferon Type I / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000556:secondary*; D008545:Melanoma / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009362:Neoplasm Metastasis
D000906:Antibodies; D006028:Glycosphingolipids; D006183:H-2 Antigens; D007370:Interferon Type I; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside