Overexpression of PRDX4 Modulates Tumor Microenvironment and Promotes Urethane-Induced Lung Tumorigenesis

Author:

Zheng Jianbo12ORCID,Guo Xin13ORCID,Nakamura Yuka4,Zhou Xiaolei5,Yamaguchi Reimon6,Zhang Jing1,Ishigaki Yasuhito4,Uramoto Hidetaka7,Yamada Sohsuke13

Affiliation:

1. Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa 920-0293, Japan

2. Department of Pediatrics, Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430022, China

3. Department of Pathology, Kanazawa Medical University Hospital, Ishikawa 920-0293, Japan

4. Department of Medical Research Institute, Kanazawa Medical University, Ishikawa 920-0293, Japan

5. College of Bioscience & Bioengineering, Hebei University of Science and Technology, Shijiazhuang 050018, China

6. Department of Dermatology, Kanazawa Medical University, Ishikawa 920-0293, Japan

7. Department of Thoracic Surgery, Kanazawa Medical University, Ishikawa 920-0293, Japan

Abstract

Peroxiredoxin 4 (PRDX4), initially reported as an antioxidant, is overexpressed in lung cancer and participates in its progression. However, its role in the urethane-induced lung tumor model is undetermined. The aim of this study was to investigate the effect of PRDX4 overexpression on carcinogen-induced lung tumor development. Human PRDX4 overexpression transgenic (Tg) mice (hPRDX4+/+) and non-Tg mice were intraperitoneally injected with urethane to induce lung tumor. After 6 months, tumor formation was compared between groups and possible mechanisms for the difference in tumor development were investigated. The serum and lung PRDX4 expressions were enhanced after urethane stimulation in Tg mice. Both the average number of tumors (≥0.5 mm) and tumor diameter per mouse in the Tg group were significantly larger than in non-Tg controls, while body weight was lower in the Tg group. Compared with non-Tg controls, tumor cell proliferation was enhanced, while tumor cell apoptosis was suppressed in Tg mice. Systemic oxidative stress and oxidative stress in lung tumors were inhibited by PRDX4 overexpression. The balance of prooxidant enzymes and antioxidant enzymes was also shifted to a decreased level in Tg tumor. In lung tumor tissue, the density of microvessel penetrated into tumor was higher in the Tg group; macrophage infiltration was enhanced in Tg tumors, while there was no difference in T lymphocyte infiltration; the expressions of cytokines, including interleukin-1 beta (IL-1β) and matrix metallopeptidase 9 (MMP9), were elevated in Tg tumors, which resulted from enhanced phosphorylation of nuclear factor-κB p65 (NF-κB p65) and c-Jun, respectively. In conclusion, PRDX4 overexpression modulated tumor microenvironment and promoted tumor development in the mouse urethane-induced lung cancer model.

Funder

Natural Science Foundation of Hebei Province

Publisher

Hindawi Limited

Subject

Cell Biology,Ageing,General Medicine,Biochemistry

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3