Expression of interleukin-33 is correlated with poor prognosis of patients with squamous cell carcinoma of the tongue

Ishikawa, Kazuya; Yagi-Nakanishi, Sayaka; Nakanishi, Yosuke; Kondo, Satoru; Tsuji, Akira; Endo, Kazuhira; Wakisaka, Naohiro; Murono, Shigeyuki; Yoshizaki, Tomokazu

doi:10.1016/j.anl.2014.08.007

Cited by 50 publications

(37 citation statements)

References 36 publications

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“…Indeed, IL‐33 promotes the invasiveness of head and neck squamous cell carcinoma through mediating the invasiveness of the key tumor‐surrounding carcinoma‐associated fibroblasts (Chen et al., 2013), suggesting IL‐33 is one of the key mediators between cancer and stromal cells. As IL‐33 also induces angiogenesis and vasopermeability (Choi et al., 2009), a study in squamous cell carcinoma of the tongue suggested that IL‐33 influences the malignant potential of the tumor through the promotion of angiogenesis in the tumor microenvironment (Ishikawa et al., 2014). In our immunohistochemical staining data, we observed that IL‐33 and ST2 were highly expressed by cancer cells and also the surrounding stromal cells, suggesting there might be a close interaction between the EOC and stromal cells.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐33 predicts poor prognosis and promotes ovarian cancer cell growth and metastasis through regulating ERK and JNK signaling pathways

et al. 2015

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Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, it remains a huge challenge to understand the cellular and molecular mechanisms of the aggressive behavior of EOC cells. Here we investigated the role of an immunomodulatory cytokine IL-33 and its receptor ST2 in mediating the growth and metastasis of EOC. Our data show that both IL-33 and ST2 were highly up-regulated in EOC tumors compared with normal ovary and ovarian benign tumors, and the expression levels were further increased in tumor tissues at the metastatic site. The expression levels of IL-33 and ST2 were positively correlated with the Ki-67 expression, and negatively correlated with the patient survival time. Using EOC cell lines, we observed that cells knocked down of IL-33 gene by siRNA had reduced migratory and invasive potential, while full length human IL-33 (fl-hIL-33) promoted the invasive, migratory and proliferative capacity of EOC cells and this process could be inhibited by IL-33 decoy receptor sST2. Signaling pathway analysis suggested that IL-33 increased the phosphorylation of ERK and JNK which was blocked by sST2. Fl-hIL-33-induced increases in EOC cell migration, invasive potential and proliferation were specifically abrogated by treatment with the ERK inhibitor U0126 while JNK inhibitor SP600125 only disrupted IL-33-induced enhancement of cell viability. Taken together, our data suggest that IL-33/ST2 axis closely associates with poor prognosis of EOC patients, and it promotes ovarian cancer growth and metastasis through regulating ERK and JNK signaling pathways. Thus IL-33/ST2 might be potential prognosis markers and therapeutic targets for EOC patients.

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Section: Discussionmentioning

confidence: 99%

Interleukin‐33 predicts poor prognosis and promotes ovarian cancer cell growth and metastasis through regulating ERK and JNK signaling pathways

et al. 2015

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“…Serum IL-33 levels are increased in many cancers such as gastric cancer, HCC, head and neck cancer, breast cancer, and lung cancer (34)(35)(36)(37)(38). Both protumor and antitumor functions of IL-33 have been shown in previous studies.…”

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confidence: 85%

IL-33 Released in the Liver Inhibits Tumor Growth via Promotion of CD4+ and CD8+ T Cell Responses in Hepatocellular Carcinoma

Jin

Lei

Lin

et al. 2018

The Journal of Immunology

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IL-33 released by epithelial cells and immune cells functions as an alarmin and can induce both type 1 and type 2 immune responses. However, the role of IL-33 release in tumor development is still not clear. In this study, we examined the function of released IL-33 in murine hepatocellular carcinoma (HCC) models by hydrodynamically injecting either IL-33–expressing tumor cells or IL-33–expressing plasmids into the liver of tumor-bearing mice. Tumor growth was greatly inhibited by IL-33 release. This antitumor effect of IL-33 was dependent on suppression of tumorigenicity 2 (ST2) because it was diminished in ST2−/− mice. Moreover, HCC patients with high IL-33 expression have prolonged overall survival compared with the patients with low IL-33 expression. Further study showed that there were increased percentages and numbers of activated and effector CD4+ and CD8+ T cells in both spleen and liver in IL-33–expressing tumor-bearing mice. Moreover, IFN-γ production of the CD4+ and CD8+ T cells was upregulated in both spleen and liver by IL-33. The cytotoxicity of CTLs from IL-33–expressing mice was also enhanced. In vitro rIL-33 treatment could preferentially expand CD8+ T cells and promote CD4+ and CD8+ T cell activation and IFN-γ production. Depletion of CD4+ and CD8+ T cells diminished the antitumor activity of IL-33, suggesting that the antitumor function of released IL-33 was mediated by both CD4+ and CD8+ T cells. Taken together, we demonstrated in murine HCC models that IL-33 release could inhibit tumor development through its interaction with ST2 to promote antitumor CD4+ and CD8+ T cell responses.

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“…In patients with squamous cell carcinoma of the tongue, high expression of IL-33 or ST2 is indicative of worse prognosis. Increased IL-33 levels in these tumors also correlate with microvessels in the stroma (38). …”

Section: Main Review Textmentioning

confidence: 99%

The Role of IL-33-Dependent Inflammation in the Tumor Microenvironment

Wasmer

Krebs

2017

Front. Immunol.

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There is compelling evidence that inflammation contributes to tumorigenesis. Inflammatory mediators within the tumor microenvironment can either promote an antitumor immune response or support tumor pathogenesis. Therefore, it is critical to determine the relative contribution of tumor-associated inflammatory pathways to cancer development. Interleukin-33 (IL-33) is a member of the IL-1 family of cytokines that is released upon tissue stress or damage to operate as an alarmin. IL-33 has been primarily implicated in the induction of type-2 immune responses. However, recent findings have shown a role of IL-33 in several cancers where it may exert multiple functions. In this review, we will present the current knowledge on the role of IL-33 in the microenvironment of different tumors. We will highlight which cells produce and which cells are activated by IL-33 in cancer. Furthermore, we will explain how IL-33 modulates the tumor-associated inflammatory microenvironment to restrain or promote tumorigenesis. Finally, we will discuss the issues to be addressed first before potentially targeting the IL-33 pathway for cancer therapy.

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Expression of interleukin-33 is correlated with poor prognosis of patients with squamous cell carcinoma of the tongue

Cited by 50 publications

References 36 publications

Interleukin‐33 predicts poor prognosis and promotes ovarian cancer cell growth and metastasis through regulating ERK and JNK signaling pathways

Interleukin‐33 predicts poor prognosis and promotes ovarian cancer cell growth and metastasis through regulating ERK and JNK signaling pathways

IL-33 Released in the Liver Inhibits Tumor Growth via Promotion of CD4+ and CD8+ T Cell Responses in Hepatocellular Carcinoma

The Role of IL-33-Dependent Inflammation in the Tumor Microenvironment

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