The Low Expression of IL-37 Involved in Multiple Myeloma – Associated Angiogenesis

Li, Zun-chang; Sun, Ming-dong; Zheng, Yong-Qing; Fu, Hongjie

doi:10.12659/msm.897451

Cited by 12 publications

(19 citation statements)

References 20 publications

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“…Li et al also reported that serum IL‐37 level had a negative correlation with VEGF and Ang‐2 levels. More interestingly, the tube formation of HUVECs was suppressed by rhIL‐37 pretreatment …”

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

confidence: 96%

“…72,73 IL-37 expression was found to be lower in MM patients compared with healthy donors. 74 Moreover, IL-37 expression level is negatively associated with Ang-2 and VEGF levels. Ang-2 and VEGF are important angiogenesis factors during lymphatic and blood vessel formation.…”

Section: Multiple Myelomamentioning

confidence: 99%

“…Although the expression of IL-37 in tumor or serum was upregulated in many cancers, including breast cancer, 49 ovarian cancer, 63 and OSCC, 67 it was shown to be downregulated in NSCLS, 52 renal cell carcinoma, 64 colon cancer, 70 MM, 74 and HCC. 24 The IL-37 serum levels in RCC and MM patients were significantly lower compared with those in healthy controls; the IL-37 expression levels in tumor tissues were decreased compared with noncancerous tissues in NSCLS, colon cancer, and HCC patients.…”

Section: Il-37 Treatment Could Significantly Reduce Tumor Cell Viabilmentioning

confidence: 99%

“…More interestingly, the tube formation of HUVECs was suppressed by rhIL-37 pretreatment. 74 The possible mechanism of these contradictory findings might be (1) the concentration of IL-37. IL-37 is more active at low concentrations as IL-37 could form dimers at high concentrations.…”

Section: The Proangiogenesis and Antiangiogenesis Role Of Il-37mentioning

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 Pementioning

confidence: 96%

Section: Multiple Myelomamentioning

confidence: 99%

Section: Il-37 Treatment Could Significantly Reduce Tumor Cell Viabilmentioning

confidence: 99%

Section: The Proangiogenesis and Antiangiogenesis Role Of Il-37mentioning

confidence: 99%

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

Liu

2018

Cancer Reports

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“…In addition, it was also found that serum IL‐37 level had a negative correlation to VEGF and Ang‐2 levels. The tube formation of HUVECs was suppressed by the rhIL‐37 pretreatment . The biphasic pro‐angiogenic effect of IL‐37 might be due to its different expression level.…”

Section: The Role In Cardiovascular Diseasesmentioning

confidence: 97%

The emerging role of interleukin‐37 in cardiovascular diseases

Zhuang

et al. 2017

Immunity Inflam & Disease

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IntroductionInterleukin (IL)‐37 is a newly identified member of the IL‐1 family, and shows a growing role in a variety of diseases. This review aims at summarizing and discussing the role of IL‐37 in cardiovascular diseases.MethodsData for this review were identified by searches of MEDLINE, Embase, and PubMed using appropriate search terms.ResultsIL‐37 is a newly identified cytokine belonging to the IL‐1 family and is expressed in inflammatory immune cells and several parenchymal cells. It has potent anti‐inflammatory and immunosuppressive properties, with two mechanisms underlying this function. IL‐37 is produced as a precursor and then cleaved into mature form in the cytoplasm by caspase‐1, translocating to nucleus and suppressing the transcription of several pro‐inflammatory genes by binding SMAD‐3. Besides, IL‐37 can be secreted extracellularly, and binds to IL‐18Ra chain and recruits Toll/IL‐1R (TIR)‐8 for transducing anti‐inflammatory signaling. IL‐37 is upregulated in an inducible manner and negatively regulates signaling mediated by TLR agonists and pro‐inflammatory cytokines. The cytokine has been shown to inhibit both innate and adaptive immunological responses, exert antitumor effects, and act as a prognostic marker in a variety of autoimmune diseases.ConclusionsRecent studies have suggested that IL‐37 plays a role in cardiovascular diseases. In this review, we provide an overview of the cytokine biology, discuss recent advances made in unraveling its cardio‐protective effects, and suggest guidelines for future research.

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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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The Low Expression of IL-37 Involved in Multiple Myeloma – Associated Angiogenesis

Cited by 12 publications

References 20 publications

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

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

The emerging role of interleukin‐37 in cardiovascular diseases

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

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