Recombinant human interferon gamma exerts an anti-proliferative effect and modulates the expression of human leukocyte antigens A,B,C and DR in human urothelial cell lines.
In this study we have treated three malignant (TGrIII) and two pre-malignant (TGrII) urothelial cell lines with recombinant human interferon gamma (rHu-INF gamma). The malignant cells (HCV29-T112C1, Hu1703He and T24) were inhibited in growth by more than 50% after treatment with 100-1000 units of rHu-INF gamma/ml for 4 days as compared to untreated controls. The growth of the pre-malignant cell lines (HCV29 and Hu609) was not influenced to the same extent in the presence of rHu-INF gamma in the culture medium. Treatment with rHu-INF gamma increased the expression of monomorphic human leukocyte antigens (HLA) A,B,C as well as beta 2-microglobulin in all the cell lines tested, as demonstrated using a quantitative immunofluorescence assay. The tumourigenic cell lines increased their expression of HLA in a dose-dependent way, whereas treatment of the non-tumourigenic cells with higher concentrations of rHu-INF gamma than 10 units/ml, did not increase the HLA-A,B,C expression further. None of the cell lines expressed HLA-DR unless treated with rHu-INF gamma. No correlation between tumourigenicity and the dose of rHu-INF gamma required for "de novo" induction of HLA-DR could be demonstrated. After removal of rHu-INF gamma from the medium, the expression of HLA-DR gradually decreased in less than 14 days, indicating that the expression of HLA-DR is not constitutive but dependent upon the presence of rHu-INF gamma. We conclude that human urothelial cells grown in vitro are sensitive to the anti-proliferative and major-histocompatibility-complex-modulating effects of rHu-INF gamma, and that malignant urothelial cells are more sensitive than pre-malignant cells. Finally, our data indicate a possible role for rHu-INF gamma in the management of human bladder cancer.
Ottesen
S S
SS
Fibiger Institute, Danish Cancer Society, Copenhagen, Denmark.
Ahrenkiel
V
V
Kieler
J
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D015234:HLA-A Antigens / Q000032:analysis*; D015235:HLA-B Antigens / Q000032:analysis*; D015236:HLA-C Antigens / Q000032:analysis*; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000473:pathology; D001613:beta 2-Microglobulin / Q000032:analysis
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D007371:Interferon-gamma