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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

Inhibition of skin carcinogenesis by suppression of NF-κB dependent ITGAV and TIMP-1 expression in IL-32γ overexpressed condition

Authors: Yong Sun Lee, Chung Hee Lee, Jun Tae Bae, Kyung Tak Nam, Dae Bong Moon, Ok Kyung Hwang, Jeong Soon Choi, Tae Hoon Kim, Hyoung Ok Jun, Young Suk Jung, Dae Yeon Hwang, Sang-Bae Han, Do Young Yoon, Jin Tae Hong

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Interleukin-32 (IL-32) has been associated with various diseases. Previous studies have shown that IL-32 inhibited the development of several tumors. However, the role of IL-32γ, an isotype of IL-32, in skin carcinogenesis remains unknown.

Methods

We compared 7,12-Dimethylbenz[a]anthracene/12-O-Tetradecanoylphorbol-13-acetate (DMBA/TPA)-induced skin carcinogenesis in wild type (WT) and IL-32γ-overexpressing mice to evaluate the role of IL-32γ. We also analyzed cancer stemness and NF-κB signaling in skin cancer cell lines with or without IL-32γ expression by western blotting, quantitative real-time PCR and immunohistochemistry analysis.

Results

Carcinogen-induced tumor incidence in IL-32γ mice was significantly reduced in comparison to that in WT mice. Infiltration of inflammatory cells and the expression levels of pro-inflammatory mediators were decreased in the skin tumor tissues of IL-32γ mice compared with WT mice. Using a genome-wide association study analysis, we found that IL-32 was associated with integrin αV (ITGAV) and tissue inhibitor of metalloproteinase-1 (TIMP-1), which are critical factor for skin carcinogenesis. Reduced expression of ITGAV and TIMP-1 were identified in DMBA/TPA-induced skin tissues of IL-32γ mice compared to that in WT mice. NF-κB activity was also reduced in DMBA/TPA-induced skin tissues of IL-32γ mice. IL-32γ decreased cancer cell sphere formation and expression of stem cell markers, and increased chemotherapy-induced cancer cell death. IL-32γ also downregulated expression of ITGAV and TIMP-1, accompanied with the inhibition of NF-κB activity. In addition, IL-32γ expression with NF-κB inhibitor treatment further reduced skin inflammation, epidermal hyperplasia, and cancer cell sphere formation and downregulated expression levels of ITGAV and TIMP-1.

Conclusions

These findings indicated that IL-32γ suppressed skin carcinogenesis through the inhibition of both stemness and the inflammatory tumor microenvironment by the downregulation of TIMP-1 and ITGAV via inactivation of NF-κB signaling.
Appendix
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Metadata
Title
Inhibition of skin carcinogenesis by suppression of NF-κB dependent ITGAV and TIMP-1 expression in IL-32γ overexpressed condition
Authors
Yong Sun Lee
Chung Hee Lee
Jun Tae Bae
Kyung Tak Nam
Dae Bong Moon
Ok Kyung Hwang
Jeong Soon Choi
Tae Hoon Kim
Hyoung Ok Jun
Young Suk Jung
Dae Yeon Hwang
Sang-Bae Han
Do Young Yoon
Jin Tae Hong
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0943-8

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