Related Experiment Video
Updated: Apr 8, 2026
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Tumor-suppressive effects of natural-type interferon-β through CXCL10 in melanoma
Hikaru Kobayashi1, Yoshimasa Nobeyama1, Hidemi Nakagawa1
1Department of Dermatology, The Jikei University School of Medicine, 25-8 Nishi-shimbashi 3-chome, Minato-ku, Tokyo, Japan.
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-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.
Materials And 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.
Insights
Interferon-beta (IFN-β) suppresses melanoma progression and metastasis by up-regulating CXCL10 in lymphatic endothelial cells. This pathway inhibits melanoma cell proliferation and may overcome resistance.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Type 1 interferon is a common adjuvant therapy for melanoma.
- Interferon-beta (IFN-β) shows tumor-suppressive effects on lymphatic metastasis.
Purpose of the Study:
- Identify melanoma-suppressive molecules induced by IFN-β in lymphatic endothelial cells.
- Investigate the role of CXCL10 in IFN-β-mediated melanoma suppression.
Main Methods:
- Treated lymphatic endothelial cells, fibroblasts, and melanoma cells with IFN-β.
- Utilized microarray analysis to identify IFN-β-induced genes.
- Performed quantitative real-time PCR, ELISA, and proliferation assays.
Main Results:
- CXCL10 was identified as a key secretory protein upregulated by IFN-β.
- IFN-β induced CXCL10 in sensitive melanoma cells, reducing proliferation.
- CXCL10 knockdown rendered melanoma cells sensitive to IFN-β; CXCR3-B expression correlated with IFN-β sensitivity.
Conclusions:
- IFN-β suppresses melanoma proliferation and metastasis via CXCL10.
- CXCL10 acts as a mediator of IFN-β's anti-melanoma effects.
- Down-regulation of CXCR3-B may contribute to IFN-β resistance.
Related Concept Videos
01:27Tumor Immunotherapy
01:30Inhibitors of Viral Protein Synthesis