INTERFERON-β FROM MELANOMA CELLS SUPPRESSES THE PROLIFERATIONS OF MELANOMA CELLS IN AN AUTOCRINE MANNER

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2002-04, Vol.18 (2), p.108-115
• Main Authors: Satomi, Hisae, Wang, Binghe, Fujisawa, Hiroshi, Otsuka, Fujio
• Format: Article
• Language: English
• Subjects: Cell Division - drug effects; Cells, Cultured; DNA Primers; Humans; IFN-β/melanocytes/melanoma; Infant, Newborn; Interferon-alpha - genetics; Interferon-beta - genetics; Interferon-beta - pharmacology; Lipopolysaccharides - pharmacology; Melanocytes - drug effects; Melanocytes - immunology; Melanoma - genetics; Melanoma - immunology; Melanoma - pathology; Poly I-C - pharmacology; Polymerase Chain Reaction; Transcription, Genetic; Tumor Cells, Cultured
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.2002.1028

Interferon (IFN)-α and IFN-β 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-α or IFN-β. In the present study, we investigated the expression of IFN-α or IFN-β in human melanocytes and five melanoma cell lines: G-361, C32TG, MMAc, MEWO and VMRC-MELG at both mRNA and protein levels. Both IFN-α and IFN-β mRNA were detected in normal human melanocytes. Likewise, IFN-α mRNA was detected in all five melanoma cell lines. However, IFN-β 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-α and IFN-β was significantly upregulated. Poly I:C was not able to induce melanocytes or melanoma cells to produce detectable amounts of IFN-α protein, but able to induce a significant amount of IFN-β in melanocytes and two of the melanoma cell lines: MMAc and VMRC-MELG. Moreover, similar to exogenous IFN-α and IFN-β, poly I:C significantly inhibited the proliferation of all five melanoma cell lines. This suppressive effect was partially blocked by anti-IFN-β antibody treatment in the IFN-β-producing melanoma cell lines: MMAc and VMRC-MELG, but not in the non-IFN-β-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-β. Furthermore, melanoma cells are capable of suppressing their own proliferation via secretion of endogenous IFN-β. This finding may have important implications for melanoma therapy.