Interleukin-37 expression and its potential role in oral leukoplakia and oral squamous cell carcinoma

Lin, Lin; Wang, Jiayi; Liu, Dongjuan; Liu, Sai; Xu, Hao; Ji, Ning; Zhou, Min; Zeng, Xin; Zhang, Dunfang; Li, Jing; Chen, Qianming

doi:10.1038/srep26757

Cited by 26 publications

(27 citation statements)

References 51 publications

(71 reference statements)

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“…Recent evidences have suggested that IL‐1R8 is a crucial checkpoint molecular in NK cells in antitumor immunity . Both IL‐37 and IL‐18Rα expressions in the tumor were upregulated in OSCC patients, indicating that IL‐37 and its receptor had similar expression pattern in cancer . The expression of IL‐1R8 in colon cancer was downregulated due to exon 8 skipping, which was consistent with the finding that IL‐37 level was decreased in the tumor of colon cancer patients .…”

Section: Mechanisms Involved In Il‐37 Antitumor Effects and Future Pesupporting

confidence: 86%

“…66 Lin et al investigated the role of IL-37 in OSCC patients and found that IL-37 expression was increased in pathologically changed tissues during the oral mucosa cancerous process. 67 Low IL-37 expression level in OSCC patients was associated with high lymph node metastasis. In vitro experiments suggested that IL-37 could modulate RAW264.7 macrophage polarization through downregulating inflammatory cytokine expressions, which could contribute to its antitumor effect.…”

Section: Oral Squamous Cell Carcinomamentioning

confidence: 97%

“…OSCC was one of the most common malignancies worldwide with low survival rate and high mortality . Lin et al investigated the role of IL‐37 in OSCC patients and found that IL‐37 expression was increased in pathologically changed tissues during the oral mucosa cancerous process . Low IL‐37 expression level in OSCC patients was associated with high lymph node metastasis.…”

Section: Il‐37 In Tumormentioning

confidence: 99%

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IL‐37: An anti‐inflammatory cytokine with antitumor functions

Liu

2018

Cancer Reports

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Background IL‐37 is a newly identified IL‐1 family cytokine. Unlike other members in IL‐1 family, IL‐37 has been demonstrated to be an anti‐inflammatory cytokine in many inflammatory and autoimmune diseases. IL‐37 is regarded as a dual‐function cytokine as both the extracellular and intracellular IL‐37 are biologically functional. Extracellular IL‐37 can bind to IL‐18Rα and IL‐1R8 to form a triple complex, regulating the downstream STAT3 and PTEN signaling. Intracellular IL‐37 can interact with Smad3, translocate into nucleus, and regulate downstream target gene expressions. Recently, the role of IL‐37 in tumor development has been extensively studied. Recent findings IL‐37 has been found to play an antitumor role in various types of tumors, such as non‐small cell lung cancer, hepatocellular carcinoma, and renal cell carcinoma. Many mechanism studies have been carried out to elaborate the possible effects of IL‐37 on tumor growth, immune responses, and tumor angiogenesis. More importantly, the function of IL‐37 may be dependent on its concentration and receptor expression. It can form dimers at high concentrations to be inactivated, thus inhibiting its anti‐inflammatory function. We focused on the role of IL‐37 in various tumor types and provided the hypothesis regarding the underlying mechanisms. Conclusion IL‐37 may affect tumor development through multiple mechanisms: (1) IL‐37 directly influences tumor cell viability; (2) IL‐37 regulates the immune response to promote the antitumor immunity; and (3) IL‐37 suppresses tumor angiogenesis in the tumor microenvironment. Future studies are warranted to further investigate the mechanisms of these multifaceted functions of IL‐37 in animal models and cancer patients.

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Section: Mechanisms Involved In Il‐37 Antitumor Effects and Future Pesupporting

confidence: 86%

Section: Oral Squamous Cell Carcinomamentioning

confidence: 97%

Section: Il‐37 In Tumormentioning

confidence: 99%

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IL‐37: An anti‐inflammatory cytokine with antitumor functions

Liu

2018

Cancer Reports

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“…Recently, it has been revealed that altered expression of IL-37 contribute to the initiation and progression of cancer [29]. Wang et al [20] found that IL-37 acts as a tumor suppressor by controlling STAT3 activity in CC.…”

Section: Discussionmentioning

confidence: 99%

IL-37 suppresses hepatocellular carcinoma growth by converting pSmad3 signaling from JNK/pSmad3L/c-Myc oncogenic signaling to pSmad3C/P21 tumor-suppressive signaling

Tang

Shen

et al. 2016

Oncotarget

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IL-37 has been characterized as a fundamental inhibitor of innate immunity and a tumor suppressor in several cancers. However, the molecular mechanism of IL-37 in hepatocellular carcinoma (HCC) is largely unclear. In this study we found IL-37 expression was down-regulated in human HCC tissues and cell lines, and was negatively correlated with tumor size, vascular invasion, as well as overall-survial and disease-free survival (OS and DFS) of HCC. Multivariate Cox analysis revealed that IL-37 was an independent prognostic indicator for OS and DFS in HCC. Functional studies further showed that IL-37 overexpression significantly suppressed tumor growth by confining HCC to G2/M cell cycle arrest in vitro and in vivo. Mechanistically, we determined that IL-37 promoted Smad3 phospho-isoform signaling conversion from JNK/pSmad3L/c-Myc oncogenic signaling to pSmad3C/p21 tumor-suppressive signaling. Consistently, we detected a significant negative correlation between IL-37 expression and pSmad3L levels in a cohort of HCC biopsies; and the expression of pSmad3L predicted poorer outcome. These data highlight the importance of IL-37 in the cell proliferation and progression of HCC, and suggests that IL-37 may be a valuable biomarker for HCC prognosis.

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“…Lin L, Wang J, Liu D, Liu S, Xu H, Ji N, et al [4] were found IL-37 and its receptor IL-18Rα but not its binding partner IL-18BP have similar tissue location and expression trend in different stages of oral mucosa carcinogenesis. Overall, IL-37 can be used as a biomarker for early oral tumorigenesis and for malignant transformation risk assessment of premalignant lesions.…”

Section: Introductionmentioning

confidence: 99%