The novel role of IL-37 in prostate cancer: evidence as a promising radiosensitizer

Ding, Vivi A.; Zhu, Ziwen; Steele, Timothy A.; Wakefield, Mark R.; Xiao, Hualiang; Balabanov, Dean; Fang, Yujiang

doi:10.1007/s12032-017-1070-7

Cited by 11 publications

(24 citation statements)

References 30 publications

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“…One study found that although IL-37 had little direct effects on the viability of prostate cancer cells, it could increase their radiosensitivity by upregulating the expression of p27, Fas, and bax and downregulating the expression of cdk2. 78 This study suggested IL-37 as a promising radiosensitizing agent for prostate cancer therapy.…”

Section: Prostate Cancermentioning

confidence: 82%

“…However, prostate cancer cells can be radioresistant in most cases; thus, there is a strong need in finding a radiosensitizing agent for prostate cancer radiotherapy. One study found that although IL‐37 had little direct effects on the viability of prostate cancer cells, it could increase their radiosensitivity by upregulating the expression of p27, Fas, and bax and downregulating the expression of cdk2 . This study suggested IL‐37 as a promising radiosensitizing agent for prostate cancer therapy.…”

Section: Il‐37 In Tumormentioning

confidence: 94%

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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: Prostate Cancermentioning

confidence: 82%

Section: Il‐37 In Tumormentioning

confidence: 94%

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

Liu

2018

Cancer Reports

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“…IL‐37 is a recently discovered cytokine that has been shown to play an anti‐inflammatory role in various human diseases 13 . IL‐37 could have antitumor effects in many cancer types, including fibrosarcoma, 14 breast cancer, 15 lung cancer, 16 renal cell carcinoma, 17 oral squamous cell carcinoma, 18 cervical cancer, 19 colon cancer, 20 multiple myeloma (MM), 21 prostate cancer, 22 and hepatocellular carcinoma (HCC) 23‐25 . However, the underlying mechanisms are still not fully understood 26,27 .…”

Section: Introductionmentioning

confidence: 99%

The indirect antiangiogenic effect of IL-37 in the tumor microenvironment

Zhu

Teo

et al. 2020

Journal of Leukocyte Biology

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IL-37, a newly identified IL-1 family cytokine, has been shown to play an important role in inflammatory diseases, autoimmune diseases, and carcinogenesis. IL-37 has been suggested to suppress tumoral angiogenesis, whereas some publications showed that IL-37 promoted angiogenesis through TGF-signaling in both physiologic and pathologic conditions. Therefore, the function of IL-37 in tumoral angiogenesis is not clear and the underlying mechanism is not known.In this current study, we investigated the direct role of IL-37 on endothelial cells, as well as its indirect effect on angiogenesis through functioning on tumor cells both in vitro and in vivo. We found that IL-37 treatment directly promoted HUVEC migration and tubule formation, indicating IL-37 as a proangiogenic factor. Surprisingly, the supernatants from IL-37 overexpressing tumor cell line promoted HUVEC apoptosis and inhibited its migration and tubule formation. Furthermore, we demonstrated that IL-37 suppressed tumor angiogenesis in a murine orthotopic hepatocellular carcinoma model, suggesting its dominant antiangiogenesis role in vivo. Moreover, microarray and qPCR analysis demonstrated that IL-37 reduced the expressions of proangiogenic factors and increased the expressions of antiangiogenic factors by tumor cells. Matrix metalloproteinase (MMP)2 expression was significantly decreased by IL-37 in both cell lines and murine tumor models. MMP9 and vascular endothelial growth factor expressions were also reduced in murine tumors overexpressing IL-37, as well as in cell lines overexpressing IL-37 under hypoxic conditions. In conclusion, although IL-37 could exert direct proangiogenic effects on endothelial cells, it plays an antiangiogenic role via modulating proangiogenic and antiangiogenic factor expressions by tumor cells in the tumor microenvironment.

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“…Therefore, IL-37 may become a potential biomarker and therapeutic target for male infertility. In prostate cancer, Ding VA et al [44] found that although IL-37 has no direct effect on prostate cancer, it can serve as a potential radiosensitizer. In the prostate cancer cells (DU145 cells), the proliferation of DU145 colonies was reduced by IL-37 treatment.…”

Section: Il-37 Is Helpful For Diagnosis and Therapy In Male Reproductive System Diseasesmentioning

confidence: 99%

Role of the novel cytokine IL-37 in inflammations and tumors of human reproductive system

Zhao¹,

Qiu²,

Yang³

et al. 2018

Obstet Gynecol Rep

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IL-37 is one of the newest members of interleukin family and is also one of the most popular cytokine. It has been identified as an inhibitor of both innate and adaptive immunity in those most recently presented researches. However, the biological properties and the related mechanism of IL-37 haven't been fully characterized. Although changes of IL-37 levels in reproductive system diseases and its role in tumors were different even potentially opposite, clues have shown that IL-37 is valuable for the diagnosis and therapy of inflammatory diseases and tumors. IL-37 plays mainly an anti-inflammatory role in Adenomyosis and Endometriosis and an anti-cancer role in cervical cancer and breast cancer. Recent controversial focuses are on the areas of tumors and ovarian diseases. In this review, the roles of IL-37 in reproductive system diseases will be presented.

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The novel role of IL-37 in prostate cancer: evidence as a promising radiosensitizer

Cited by 11 publications

References 30 publications

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

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

The indirect antiangiogenic effect of IL-37 in the tumor microenvironment

Role of the novel cytokine IL-37 in inflammations and tumors of human reproductive system

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