title: Interferon-beta from melanoma cells suppresses the proliferations of melanoma cells in an autocrine manner.
abstract: Interferon (IFN)-alpha and IFN-beta have been utilized in the treatment of melanoma as a form of cytokine therapy. While previous studies have demonstrated that melanocytes and melanoma cells produce a number of cytokines, it remains unclear whether or not melanocytes and melanoma cells per se produce IFN-alpha or IFN-beta. In the present study, we investigated the expression of IFN-alpha or IFN-beta in human melanocytes and five melanoma cell lines: G-361, C32TG, MMAc, MEWO and VMRC-MELG at both mRNA and protein levels. Both IFN-alpha and IFN-beta mRNA were detected in normal human melanocytes. Likewise, IFN-alpha mRNA was detected in all five melanoma cell lines. However, IFN-beta mRNA was only detected in one melanoma cell line, VMRC-MELG. When melanocytes and melanoma cells were treated with a potent IFN inducer, polyinosinic:polycytidylic acid (poly I:C), the mRNA expression of both IFN-alpha and IFN-beta was significantly upregulated. Poly I:C was not able to induce melanocytes or melanoma cells to produce detectable amounts of IFN-alpha protein, but able to induce a significant amount of IFN-beta in melanocytes and two of the melanoma cell lines: MMAc and VMRC-MELG. Moreover, similar to exogenous IFN-alpha and IFN-beta, poly I:C significantly inhibited the proliferation of all five melanoma cell lines. This suppressive effect was partially blocked by anti-IFN-beta antibody treatment in the IFN-beta-producing melanoma cell lines: MMAc and VMRC-MELG, but not in the non-IFN-beta-producing cell lines: G-361, C32TG and MEWO. Collectively, these studies have demonstrated for the first time that human melanocytes and melanoma cells produce IFN-beta. Furthermore, melanoma cells are capable of suppressing their own proliferation via secretion of endogenous IFN-beta. This finding may have important implications for melanoma therapy.
authors.affiliation: Department of Dermatology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Hisae
authors.initials: H
authors.lastname: Satomi
authors.forename: Binghe
authors.initials: B
authors.lastname: Wang
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Fujio
authors.initials: F
authors.lastname: Otsuka
mesh_terms: D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D017931:DNA Primers; D006801:Humans; D007231:Infant, Newborn; D016898:Interferon-alpha / Q000235:genetics; D016899:Interferon-beta / Q000235:genetics* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008544:Melanocytes / Q000187:drug effects / Q000276:immunology; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D011070:Poly I-C / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D016899:Interferon-beta; D011070:Poly I-C