Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

Andreone, Sara; Gambardella, Adriana; Mancini, Jacopo; Loffredo, Stefania; Marcella, Simone; Sorsa, Valentina La; Varricchi, Gilda; Schiavoni, Giovanna; Mattei, Fabrizio

doi:10.3389/fimmu.2020.571593

Cited by 27 publications

(28 citation statements)

References 102 publications

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“…The cells comprised of the tumor microenvironment are a great source of IL-33 indicated to have antitumorigenic and pro-tumorigenic roles in cancer formation and progression [8]. IL-33, a member of the IL-1 family of cytokines, can act through binding a heterodimer formed by its primary receptor ST2 and the co-receptor IL-1 receptor accessory protein (IL1RAP) [8]. IL-33/ST2 axis activates NF-kB, c-Jun N-terminal kinase (JNK), and mitogen-activated protein kinase (MAPK) in cells involved in Th2 response [8].…”

Section: Discussionmentioning

confidence: 99%

“…IL-33, a member of the IL-1 family of cytokines, can act through binding a heterodimer formed by its primary receptor ST2 and the co-receptor IL-1 receptor accessory protein (IL1RAP) [8]. IL-33/ST2 axis activates NF-kB, c-Jun N-terminal kinase (JNK), and mitogen-activated protein kinase (MAPK) in cells involved in Th2 response [8]. In the central nervous system (CNS), Yasuoka et al revealed the expression of IL-33 by endothelial cells and astrocytes and its receptors on astrocytes and microglia.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, IL-33, a member of the IL-1 cytokine family [5], has been revealed as an essential regulator of the glioma microenvironment by promoting the secretion of various in ammatory cytokines from glioma cells and recruiting tumor-associated macrophages (TAMs), microglia and other immune cells [6]. IL-33, also involved in immune response and infection, has a dual effect on tumor stromal cells and tumor cells that it can perform both as a cytokine through binding and activating the ST2 receptor and act as a transcriptional regulator [7][8][9]. Furthermore, IL-33 has been revealed to promote tumor cell migration and invasion via inducing epithelial to mesenchymal differentiation and regulating protease activity of tumor cells for degradation of extracellular matrix (ECM) in colorectal cancer, pancreatic cancer, melanoma, and glioma [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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IL-33 induces ADAMTS5 expression and cell migration in glioblastoma multiforme

et al. 2022

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Glioblastoma multiforme (GBM), characterized by a high rate of proliferation and migration capacity, is an incurable brain tumor in adults. , a member of the IL-1 cytokine superfamily and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), a family of zinc dependent metalloproteinases are known to have an essential roles in GBM migration and invasion. Previous studies have separately revealed elevated expressions of IL-33 and ADAMTS5 in GBM; however, the interaction between IL-33 and ADAMTS5 in GBM pathogenesis has remained unclear. Here, using publically available GlioVis and GEPIA programs, we showed that mRNA expression of IL-33 and ADAMTS5 is signi cantly high in GBM cells, and a positive correlation between IL-33 and ADAMTS5 was also determined in these cells. In parallel with the mRNA data of IL-33 and ADAMTS5, by Western blot analysis, protein levels were found to be elevated in GBM tissues and increased gradually with the disease progression. Primary GBM cells and low-grade glioma cells were then treated with IL-33 to examine its stimulating effect on ADAMTS5 expression. Exposure to IL-33 raised ADAMTS5 protein levels in a dose-dependent manner. Finally, the wound healing method was performed to con rm the impact of IL-33 on migration in primary GBM cells. IL-33 promoted migration of primary GBM cells three-times higher than untreated GBM cells. Thus, the current study suggests for the rst time that IL-33 might have a role in play a part in GBM progression through induction of ADAMTS5 expression and promotion of migration in GBM cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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IL-33 induces ADAMTS5 expression and cell migration in glioblastoma multiforme

et al. 2022

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“…Sema4A is identified as a biomarker for DC activation status, especially in the human immune system (69). IL-33, as a candidate for cytokine therapies, can effectively enhance Sema4A expression and stimulate anti-tumoral cells including NK and CD8 + T cells (29,94), while the mechanism of IL-33 on anti-tumor effects remains unclear. Sema4A on DC interacting with its Plexin B2 receptor on CTL can promote INF-g production, increase the cytotoxicity of CTLs, and repress tumor growth (29).…”

Section: Sema4amentioning

confidence: 99%

Semaphorins as Potential Immune Therapeutic Targets for Cancer

et al. 2022

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Semaphorins are a large class of secreted or membrane-bound molecules. It has been reported that semaphorins play important roles in regulating several hallmarks of cancer, including angiogenesis, metastasis, and immune evasion. Semaphorins and their receptors are widely expressed on tumor cells and immune cells. However, the biological role of semaphorins in tumor immune microenvironment is intricate. The dysregulation of semaphorins influences the recruitment and infiltration of immune cells, leading to abnormal anti-tumor effect. Although the underlying mechanisms of semaphorins on regulating tumor-infiltrating immune cell activation and functions are not fully understood, semaphorins can notably be promising immunotherapy targets for cancer.

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“…Emerging studies have proved the positive role of eosinophils in mediating anticancer immunity-related counteractivity by IL-33 within several cancers, including CRC[ 71 ]. A more recent study by Kienzl and colleagues demonstrated that IL-33 can inhibit cancer expansion in CT26 engraftment/colitis-linked CRC mouse models[ 72 ].…”

Section: Diversified Therapeutics Based On Il-33/st2 Signaling In Crcmentioning

confidence: 99%

Paradoxical role of interleukin-33/suppressor of tumorigenicity 2 in colorectal carcinogenesis: Progress and therapeutic potential

Huang¹,

Chen²,

Ma³

et al. 2022

WJCC

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Colorectal cancer (CRC) is presently the second most prevalent global mortality-inducing cancer. CRC carcinogenesis is a multifactorial process involving internal genetic mutations and the external environment. In addition, non-neoplastic cell activities within tumor microenvironments for CRC development have been established. However, interleukin (IL)-33, secreted by such cell types, plays a pivotal role in cancer progression due to interaction with cellular constituents within the tumor-inflammation microenvironment. IL-33 belongs to the IL-1 cytokine family and acts as binding attachments for the suppressor of tumorigenicity (ST)2 receptor. Therefore, how to coordinate tumor microenvironment, design and optimize treatment strategies suitable for CRC, based on IL-33/ST2 signal is a challenge. Even though it has established influences upon immunity-linked conditions, IL-33 effects on CRC progression and prevention and related mechanisms are still controversial. Our review depicts controversial activities for IL-33/ST2 within carcinogenesis and cancer prevention. Moreover, IL-33/ST2 signaling is a potential therapeutic target for CRC.

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Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight

Cited by 27 publications

References 102 publications

IL-33 induces ADAMTS5 expression and cell migration in glioblastoma multiforme

IL-33 induces ADAMTS5 expression and cell migration in glioblastoma multiforme

Semaphorins as Potential Immune Therapeutic Targets for Cancer

Paradoxical role of interleukin-33/suppressor of tumorigenicity 2 in colorectal carcinogenesis: Progress and therapeutic potential

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