Regulation of the antigenic phenotype of human melanoma cells by recombinant interferons. 1986

P Giacomini, and R Gambari, and R Barbieri, and P Nisticò, and R Tecce, and S Pestka, and K Gustafsson, and P G Natali, and P B Fisher

The ability of interferons to modulate the antigenic phenotype of tumor cells may involve alterations in the transcription, translation, membrane expression and shedding of Major Histocompatibility Complex (MHC) and Tumor Associated Antigens (TAAs). In the present study we have investigated possible mechanisms by which recombinant human interferons, IFN-alpha, -beta and -gamma, alter the antigenic profile of long- and short-term human melanoma cultures. IFN-alpha and -beta induced similar changes in the synthesis, expression and shedding of two TAAs, a HMW-MAA and a Cyt-MAA, in the established melanoma cell line Colo 38, whereas IFN-gamma exerted a differential effect on these melanoma associated antigens. Moreover, IFN-gamma was relatively more effective than IFN-alpha or -beta in upregulating the synthesis, expression and shedding of class I MHC antigens. At the same time a dramatic differential effect of the interferons was observed with class II MHC antigens. IFN-alpha or -beta induced a modest increase in the synthesis and expression of these antigens, whereas IFN-gamma was greater than 3-fold more active in inducing the synthesis and expression of DR/DP antigens and greater than 4- and greater than 10-fold more effective in increasing the synthesis and expression, respectively, of DQ antigens. Analysis of the levels of cytoplasmic mRNA for the DR-alpha and DQ-beta genes indicated no significant difference between IFN-alpha, beta or -gamma treated cells suggesting that IFN-gamma enhancement of the synthesis of DR and DQ antigens may occur at a posttranscriptional level. In the case of a newly established human melanoma cell line (MG-3) IFN-gamma enhanced the synthesis but not the expression of DR antigens and did not alter either the synthesis or expression of DQ antigens. Our studies indicate that the effects of interferons on the antigenic phenotype of melanoma cells will vary depending on the type of interferon employed, the antigen monitored and the target cell studied. In addition, it is also apparent that some of the biosynthetic steps involved in regulating the synthesis, expression and shedding of antigens may be coordinately regulated in some melanoma cells, whereas these processes may be under independent control in other melanoma populations.

UI MeSH Term Description Entries
D007370 Interferon Type I Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA). Interferons Type I,Type I Interferon,Type I Interferons,Interferon, Type I,Interferons, Type I
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D007372 Interferons Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. Interferon
D008285 Major Histocompatibility Complex The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. Histocompatibility Complex,Complex, Histocompatibility,Complex, Major Histocompatibility,Complices, Histocompatibility,Complices, Major Histocompatibility,Histocompatibility Complex, Major,Histocompatibility Complices,Histocompatibility Complices, Major,Major Histocompatibility Complices
D008545 Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445) Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression

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