Interleukin-1 receptor antagonist (IL1RN) is associated with suppression of early carcinogenic events in human oral malignancies

Shiiba,Masashi; Saito,Kengo; Yamagami,Hitomi; Nakashima,Dai; Higo,Morihiro; Kasamatsu,Atsushi; Sakamoto,Yosuke; Ogawara,Katsunori; Uzawa,Katsuhiro; Takiguchi,Yuichi; Tanzawa,Hideki

doi:10.3892/ijo.2015.2917

Interleukin-1 receptor antagonist (IL1RN) is associated with suppression of early carcinogenic events in human oral malignancies

Authors:
- Masashi Shiiba
- Kengo Saito
- Hitomi Yamagami
- Dai Nakashima
- Morihiro Higo
- Atsushi Kasamatsu
- Yosuke Sakamoto
- Katsunori Ogawara
- Katsuhiro Uzawa
- Yuichi Takiguchi
- Hideki Tanzawa
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Affiliations: Department of Oral Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan, Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan
Published online on: March 4, 2015 https://doi.org/10.3892/ijo.2015.2917
Pages: 1978-1984

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Abstract

Inflammatory abnormalities have been implicated in the pathogenesis of various human diseases, including cancer. Interleukin-1 receptor antagonist (IL1RN) is a potent anti-inflammatory molecule that modulates the biological activity of the proinflammatory cytokine, interleukin-1. The aim of this study was to examine the expression of IL1RN in oral squamous cell carcinomas (OSCCs), and to determine its clinical significance. Expression levels of IL1RN in matched normal and tumor specimens from 39 OSCCs were evaluated using real-time quantitative polymerase chain reaction methods, and immunohistochemical analysis. Protein expression of IL1RN was also examined in 18 oral premalignant lesions (OPLs). Expression of IL1RN mRNA was significantly downregulated in OSCCs compared with normal tissues. Decreased expression of IL1RN protein was also observed in OPLs and OSCCs. The IL1RN expression level was lower in the OPL cases with severe dysplasia compared to those with mild/moderate dysplasia. Significantly downregulated IL1RN expression was observed in all OSCC lesion sites examined when compared with the matched normal tissues. However, the decreased level of IL1RN expression did not correspond with tumor progression. Noteworthy, IL1RN expression was higher in the advanced OSCC cases (T3/T4) compared to early cases (T1/T2). Among OSCC samples, relatively higher IL1RN expression was associated with active tumor development in the OSCCs occurring in the buccal mucosa, oral floor, fauces and gingiva, but not the tongue. These data suggest that IL1RN may exhibit opposing characteristics in oral malignancies depending on the stage of cancer development, suppressing early carcinogenic events, yet promoting tumor development in some lesion sites. Thus, IL1RN could represent a reliable biomarker for the early diagnosis of OSCCs. Furthermore, IL1RN may possess unknown and complex functions in the developed OSCC.

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