title: Tumor-suppressive effects of natural-type interferon-β through CXCL10 in melanoma.
abstract: BACKGROUND
  Type 1 interferon is in widespread use as adjuvant therapy to inhibit melanoma progression. Considering the tumor-suppressive effects of local administration of interferon-β (IFN-β) on lymphatic metastasis, the present study was conducted to identify melanoma-suppressive molecules that are up-regulated by IFN-β treatment of lymphatic endothelial cells.
  
  
  METHODS
  Lymphatic endothelial cells, fibroblasts, and melanoma cells were treated with natural-type IFN-β, and melanoma cells were treated with CXCL10. Genome-wide oligonucleotide microarray analysis was performed using lymphatic endothelial cells with or without IFN-β treatment. Quantitative real-time reverse transcription-PCR and an enzyme-linked immunosorbent assay were performed to examine CXCL10 expression. A proliferation assay was performed to examine the effects of IFN-β and CXCL10 in melanoma cells.
  
  
  RESULTS
  Genome-wide microarray analyses detected CXCL10 as a gene encoding a secretory protein that was up-regulated by IFN-β in lymphatic endothelial cells. IFN-β treatment significantly induced CXCL10 in dermal lymphatic endothelial cells and melanoma cells that are highly sensitive to IFN-β. CXCL10 reduced melanoma cell proliferation in IFN-β-sensitive cells as well as resistant cells. Melanoma cells in which CXCL10 was knocked down were sensitive to IFN-β. CXCR3-B, which encodes the CXCL10 receptor, was up-regulated in melanoma cells with high sensitivity to IFN-β and down-regulated in melanoma cells with medium to low sensitivity.
  
  
  CONCLUSIONS
  Our data suggest that IFN-β suppresses proliferation and metastasis from the local lymphatic system and melanoma cells via CXCL10. Down-regulation of CXCR3-B by IFN-β may be associated with resistance to IFN-β.
authors.affiliation: Department of Dermatology, The Jikei University School of Medicine, 25-8 Nishi-shimbashi 3-chome, Minato-ku, Tokyo, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Dermatology, The Jikei University School of Medicine, 25-8 Nishi-shimbashi 3-chome, Minato-ku, Tokyo, Japan. Electronic address: nobederm@jikei.ac.jp.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Nobeyama
authors.affiliation: Department of Dermatology, The Jikei University School of Medicine, 25-8 Nishi-shimbashi 3-chome, Minato-ku, Tokyo, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Nakagawa
mesh_terms: D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D016899:Interferon-beta / Q000502:physiology*; D008545:Melanoma / Q000473:pathology*; D054367:Receptors, CXCR3 / Q000502:physiology; D015854:Up-Regulation
chemical_list: C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054367:Receptors, CXCR3; D016899:Interferon-beta
keywords: CXCL10; Chemokine (C-X-C motif) ligand 10; Interferon-β; Melanoma; Tumor microenvironment