Increased expression of versican in the inflammatory response to UVB- and reactive oxygen species-induced skin tumorigenesis

Makoto Kunisada, Flandiana Yogianti, Sakumi Kunihiko, Ryusuke Ono, Yusaku Nakabeppu, Chikako Nishigori

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Excessive exposure to UV radiation is a major risk factor for developing skin cancer. UV-induced reactive oxygen species (ROS) cause accumulation of DNA damage products such as 8-oxoguanine (8-oxoG) in the skin. We have previously shown that mice lacking the repair enzyme 8-oxoguanine glycosylase (Ogg1 knockout mice) are highly susceptible to skin cancer after long-term UVB exposure. To investigate the genes involved, we performed gene profiling of Ogg1 knockout mouse skin after UVB exposure. Among the up-regulated genes in UVB-treated Ogg1 knockout mice, inflammatory response pathway-related genes were most affected. The Vcan gene, which encodes the large extracellular matrix proteoglycan versican, was continuously up-regulated in UVB-treated Ogg1 knockout mice, suggesting that versican is a mediator of skin cancer development. We examined the expression pattern of versican in skin tumors from wild-type mice and UVB-treated Ogg1 knockout mice, and also analyzed 157 sun-related human skin tumors. Versican was strongly expressed in malignant skin tumors in both mice and humans, and especially in Ogg1 knockout mice. Additionally, infiltrating neutrophils strongly colocalized with versican in UVB-treated Ogg1 knockout mouse skin. These data demonstrate that inflammatory responses, particularly neutrophil infiltration and versican up-regulation, are closely involved in UVB/ROS-induced skin tumorigenesis.

Original languageEnglish
Pages (from-to)3056-3065
Number of pages10
JournalAmerican Journal of Pathology
Volume179
Issue number6
DOIs
Publication statusPublished - Dec 1 2011

Fingerprint

Versicans
Knockout Mice
Reactive Oxygen Species
Carcinogenesis
Skin
Skin Neoplasms
Genes
Neoplasms
Neutrophil Infiltration
Solar System
Proteoglycans
DNA Damage
Extracellular Matrix
Neutrophils
Up-Regulation
Radiation
Enzymes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Increased expression of versican in the inflammatory response to UVB- and reactive oxygen species-induced skin tumorigenesis. / Kunisada, Makoto; Yogianti, Flandiana; Kunihiko, Sakumi; Ono, Ryusuke; Nakabeppu, Yusaku; Nishigori, Chikako.

In: American Journal of Pathology, Vol. 179, No. 6, 01.12.2011, p. 3056-3065.

Research output: Contribution to journalArticle

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