BACKGROUND: Type 1 interferons (IFNs), including IFN-â, are widely used in adjuvant therapy for patients who undergo surgery for malignant melanoma to inhibit recurrence and in-transit metastasis. The precise mechanisms underlying the tumor-suppressive effects of IFN-â on melanoma are not yet completely understood.OBJECTIVE: The purpose was to reveal the mechanisms underlying the tumor-suppressive effects of IFN-â via interleukin (IL)-24.METHODS: Genome-wide oligonucleotide microarray, quantitative real-time reverse transcription-polymerase chain reaction (PCR), enzyme-linked immunosorbent assay and western blotting assay were performed using four melanoma cell lines (A375, RPMI-7951, SK-MEL-5 and SK-MEL-1) treated with natural-type IFN-â to assess the expression of IL-24. Proliferation assay was performed using these melanoma cells and IL-24 knock-down melanoma cells.RESULTS: Genome-wide microarray analysis detected candidate genes upregulated in IFN-â-sensitive cells after treatment with IFN-â. We focused on IL-24 among the candidate genes encoding secretory proteins. Peak IL-24 mRNA expression completely correlated with the order of sensitivity of melanoma cells to IFN-â. IFN-â treatment induced extracellular IL-24 protein in IFN-â-sensitive cells, but did not induce intracellular IL-24 protein. Knock-down of IL-24 changed melanoma cells into IFN-â-resistant cells. The expression ratio of IL-22R1, one of the IL-24 receptors, correlated with the order of sensitivity of melanoma cells to IFN-â. Treatment with recombinant human IL-24 did not have any effects on all the melanoma cell lines.CONCLUSION: Our data suggest that IFN-â suppresses the proliferation of melanoma cells through extracellular IL-24 protein derived from melanoma cells.
Apoptosis Cell Line, Tumor