화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.464, No.2, 416-421, 2015
Tumor-suppressive effects of natural-type interferon-beta through CXCL10 in melanoma
Introduction: Type 1 interferon is in widespread use as adjuvant therapy to inhibit melanoma progression. Considering the tumor-suppressive effects of local administration of interferon-beta (IFN-beta) on lymphatic metastasis, the present study was conducted to identify melanoma-suppressive molecules that are up-regulated by IFN-beta treatment of lymphatic endothelial cells. Materials and methods: Lymphatic endothelial cells, fibroblasts, and melanoma cells were treated with natural-type IFN-beta, and melanoma cells were treated with CXCL10. Genome-wide oligonucleotide microarray analysis was performed using lymphatic endothelial cells with or without IFN-beta 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-beta 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-beta in lymphatic endothelial cells. IFN-beta treatment significantly induced CXCL10 in dermal lymphatic endothelial cells and melanoma cells that are highly sensitive to IFN-beta. CXCL10 reduced melanoma cell proliferation in IFN-beta-sensitive cells as well as resistant cells. Melanoma cells in which CXCL10 was knocked down were sensitive to IFN-beta. CXCR3-B, which encodes the CXCL10 receptor, was up-regulated in melanoma cells with high sensitivity to IFN-beta and down-regulated in melanoma cells with medium to low sensitivity. Conclusions: Our data suggest that IFN-beta suppresses proliferation and metastasis from the local lymphatic system and melanoma cells via CXCL10. Down-regulation of CXCR3-B by IFN-beta may be associated with resistance to IFN-beta. (C) 2015 Elsevier Inc. All rights reserved.