The predictive value of transforming growth factor-β in Wilms tumor immunopathogenesis

Amarante, Marla Karine; Oliveira, Carlos Eduardo Coral de; Ariza, Carolina Batista; Sakaguchi, Alberto Yoichi; Ishibashi, Cintya Mayumi; Watanabe, Maria Angélica Ehara

doi:10.1080/08830185.2017.1291639

Cited by 9 publications

(8 citation statements)

References 65 publications

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“…The dysregulation of TGF-β has been linked to the initiation and progression of multiple human cancers, including WT [18]. Several studies have demonstrated that the TGFβ signaling was activated by TGF-β; the ligands lead to the Negative expression of TGF-β1 and P-Smad2/3 proteins.…”

Section: Discussionmentioning

confidence: 99%

“…In pediatric tumors, particularly WT, abnormally activated TGF-β signaling may be an important mediator of tumor cell growth, and the positive expression of TGF-β in WT was associated with tumor anaplastic, invasion, and disease progression [15][16][17]. Although TGF-β signaling played a key role in WT, the molecular mechanisms behind this regulation are unknown [18].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Wilms’ Tumor Proliferation and Invasion by Blocking TGF-β Receptor I in the TGF-β/Smad Signaling Pathway

Shi

et al. 2020

BioMed Research International

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Wilms’ tumor (WT) is a common embryonal tumor, and nephrogenic rests play a critical role in WT development. The transforming growth factor β (TGF-β) signaling pathway is fundamental to embryo development and cell growth and proliferation. Moreover, TGF-β contributes to WT development, but the mechanisms of disease pathogenicity are unknown. This study investigated whether the TGF-β signaling pathway was involved in WT and whether blocking TβRI receptor inhibited WT growth, proliferation, and invasion. A total of 60 WT patients with clinical data and surgical specimens were evaluated. Immunohistochemistry (IHC) was used to detect the expression of TGF-β1 and P-smad2/3. In vitro, the proliferation, migration, apoptosis, and epithelial-mesenchymal transition (EMT) protein expression were analyzed using the CCK8 assay, wound healing assay, transwell assay, flow cytometry, and western blot, respectively. In vivo, tumor morphology, tumor size, toxicity, and EMT protein expression were analyzed in tumor-bearing mice treated with a TβRI kinase inhibitor or PBS. High protein levels of TGF-β1 and P-samd2/3 were associated with clinical stage and metastasis or invasion. TβRI inhibition effectively suppressed WT proliferation and migration and promoted apoptosis in the human WT cell line G401, consequently decreasing EMT protein expression. In addition, the TβRI kinase inhibitor significantly impaired the subcutaneous growth of WT. It is worth noting that treatment with the TβRI kinase inhibitor did not cause liver and kidney injury. Our results indicate that the TGF-β/Smad signaling pathway plays a crucial role in WT progression. Blocking the TβRI receptor may be a novel strategy to treat and prevent WT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of Wilms’ Tumor Proliferation and Invasion by Blocking TGF-β Receptor I in the TGF-β/Smad Signaling Pathway

Shi

et al. 2020

BioMed Research International

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“… 62 Correspondingly, the tumor microenvironment of WT is also characterized by a high production of immunosuppressive cytokines, of which TGF-β appears to have the most dominant role in tumor progression. 62 , 63 , 64 , 65 Its role in kidney development and renal architecture control might explain its expression in a malignant kidney tumor. Moreover, high TGF-β levels are generally associated with epithelial-to-mesenchymal transition (EMT) mediated by E-cadherin downregulation.…”

Section: Cytokine Productionmentioning

confidence: 99%

“…64 A further tumor-promoting role of TGF-b in Wilms is the fact that this cytokine induces Forkhead box P3 (FOXP3) expression on T-reg cells. 65 This is a transcription factor known to be crucial in conferring immunosuppressive functions to the T-regs. 66 Correspondingly, FOXP3+ T-reg cells have been described to be diffusely present in WTs, and their infiltration is significantly higher than in control kidneys.…”

Section: Cytokine Productionmentioning

confidence: 99%

Systematic review of the immunological landscape of Wilms tumors

Palmisani

Kovar

Kager

et al. 2021

Molecular Therapy - Oncolytics

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Results of immunotherapy in childhood solid cancer have been so far, with the exception of neuroblastoma, quite disappointing. Lack of knowledge of the immune contexture of these tumors may have contributed to the failure of immunotherapies so far. Here, we systematically reviewed the literature regarding the immunology of Wilms tumor (WT), one of the most frequent pediatric solid tumors of the abdomen. In Wilms tumor patients the high cure rate of >90%, achieved by the combination of surgery and radio-chemotherapy, is at the expense of a high early and late toxicity. Moreover, treatment-resistant entities, such as diffuse anaplastic tumors or recurrent disease, still pose unsolved clinical problems. Successful immunotherapy could represent a novel and possibly less-toxic treatment option. Employing the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) method of literature search, we analyzed the current knowledge of the immunological landscape of Wilms tumors in terms of tumor microenvironment, prognostic implications of single biomarkers, and immunotherapy response.

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“…TGFBRI is a serine/threonine kinase receptor that is a member of the TGF-β signaling pathway, and exhibits metastatic properties by invading surrounding cells [13]. Previous reports have indicated that the TGF-β and IGF signaling pathways are associated with the development of nephroblastoma [14, 15]. However, the roles of TGFBRI and IGF1R in the progress of nephroblastoma require further investigation.…”

Section: Introductionmentioning

confidence: 99%

miR-140-5p could suppress tumor proliferation and progression by targeting TGFBRI/SMAD2/3 and IGF-1R/AKT signaling pathways in Wilms’ tumor

Liu

Ouyang

et al. 2019

BMC Cancer

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Background: Wilms' tumor is also called nephroblastoma and is the most common pediatric renal cancer. Several genetic and epigenetic factors have been found to account for the development of Wilms' tumor. MiRNAs play important roles in this tumorigenic process. In the present study, we aimed to investigate the role of miR-140-5p in nephroblastoma by identifying its targets, as well as its underlying molecular mechanism of action. Methods: The miRNA expression profile of nephroblastoma samples was investigated and the targets of miR-140-5p were predicted and validated using the miRNA luciferase reporter method. Moreover, the roles of miR-140-5p in regulating nephroblastoma cell proliferation, migration and cell cycle were analyzed by the CCK8, migration and flow cytometry assays, respectively. The downstream protein of the direct target of miR-140-5p was also identified. Results: miR-140-5p was downregulated in Wilms' tumor tissues, whereas in the nephroblastoma cell lines G401 and WT-CLS1 that exhibited high levels of miRNA-140-5p, inhibition of cellular proliferation and metastasis were noted as well as cell cycle arrest at the G1/S phase. TGFBRI and IGF1R were identified as direct target genes for miRNA-140-5p. In addition, SMAD2/3 and p-AKT were regulated by TGFBRI and IGF1R separately and participated in the miRNA-140-5p regulatory network. Ectopic expression of TGFBR1 and IGF-1R could abrogate the inhibitory effect of miR-140-5p. Conclusion: We demonstrated that miRNA-140-5p participates in the progression of Wilms' tumor by targeting the TGFBRI/SMAD2/3 and the IGF-1R/AKT signaling pathways.

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The predictive value of transforming growth factor-β in Wilms tumor immunopathogenesis

Cited by 9 publications

References 65 publications

Inhibition of Wilms’ Tumor Proliferation and Invasion by Blocking TGF-β Receptor I in the TGF-β/Smad Signaling Pathway

Inhibition of Wilms’ Tumor Proliferation and Invasion by Blocking TGF-β Receptor I in the TGF-β/Smad Signaling Pathway

Systematic review of the immunological landscape of Wilms tumors

miR-140-5p could suppress tumor proliferation and progression by targeting TGFBRI/SMAD2/3 and IGF-1R/AKT signaling pathways in Wilms’ tumor

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