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Role of interleukin‐24 in the tumor‐suppressive effects of interferon‐β on melanoma
Author(s) -
Watanabe Yoshinori,
Itoh Munenari,
Nakagawa Hidemi,
Asahina Akihiko,
Nobeyama Yoshimasa
Publication year - 2019
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13955
Subject(s) - melanoma , cancer research , biology , interferon , microarray analysis techniques , cell culture , microbiology and biotechnology , downregulation and upregulation , immunology , gene expression , gene , biochemistry , genetics
Background Type 1 interferons (IFNs), including IFN‐β, 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‐β on melanoma are not yet completely understood. Objective The purpose was to reveal the mechanisms underlying the tumor‐suppressive effects of IFN‐β 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‐β 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‐β‐sensitive cells after treatment with IFN‐β. 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‐β. IFN‐β treatment induced extracellular IL‐24 protein in IFN‐β‐sensitive cells, but did not induce intracellular IL‐24 protein. Knock‐down of IL‐24 changed melanoma cells into IFN‐β‐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‐β. Treatment with recombinant human IL‐24 did not have any effects on all the melanoma cell lines. Conclusion Our data suggest that IFN‐β suppresses the proliferation of melanoma cells through extracellular IL‐24 protein derived from melanoma cells.