Down-regulation of Aquaporin-1 mediates a microglial phenotype switch affecting glioma growth

Hu, Feng; Huang, Yimin; Semtner, Marcus; Zhao, Kai; Tan, Zhoubin; Dzaye, Omar; Kettenmann, Helmut; Shu, Kai; Lei, Ting

doi:10.1016/j.yexcr.2020.112323

Cited by 8 publications

(5 citation statements)

References 34 publications

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“…Indeed, the obtained results showed that the τ in decrease and the AQP1 and the AQP4 overexpression are hallmarks in the case of invasion/migration. While the role of the AQP1 in glioma invasion/migration was studied by few groups [ 32 , 36 , 37 ], the role of the AQP4 is well established, as recently reviewed by Vandebroek et al [ 16 ]. In the present study, new evidence is robustly demonstrated by using relevant mouse models of glioma invasion/migration.…”

Section: Resultsmentioning

confidence: 99%

Role of Transmembrane Water Exchange in Glioma Invasion/Migration: In Vivo Preclinical Study by Relaxometry at Very Low Magnetic Field

Ruggiero

Itto

Baroni

et al. 2022

Cancers

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This work shows that the longitudinal relaxation differences observed at very low magnetic fields between invasion/migration and proliferation processes on glioma mouse models in vivo are related to differences in the transmembrane water exchange basically linked to the aquaporin expression changes. Three glioma mouse models were used: Glio6 and Glio96 as invasion/migration models and U87 as cell proliferation model. In vivo proton longitudinal relaxation-rate constants (R1) at very low fields were measured by fast field cycling NMR (FFC-NMR). The tumor contribution to the observed proton relaxation rate, R1tum (U87: 12.26 ± 0.64 s−1; Glio6: 3.76 ± 0.88 s−1; Glio96: 6.90 ± 0.64 s−1 at 0.01 MHz), and the intracellular water lifetime, τin (U87: 826 ± 19 ms; Glio6: 516 ± 8 ms; Glio96: 596 ± 15 ms), were found to be good diagnostic hallmarks to distinguish invasion/migration from proliferation (p < 0.01 and 0.001). Overexpression of AQP4 and AQP1 were assessed in invasion/migration models, highlighting the pathophysiological role of these two aquaporins in water exchange that, in turn, determine the lower values in the observed R1 relaxation rate constant in glioma invasion/migration. Overall, our findings demonstrate that τin and R1 (measured at very low fields) are relevant biomarkers, discriminating invasion/migration from proliferation in vivo. These results highlight the use of FFC-NMR and FFC-imaging to assess the efficiency of drugs that could modulate aquaporin functions.

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Section: Resultsmentioning

confidence: 99%

Role of Transmembrane Water Exchange in Glioma Invasion/Migration: In Vivo Preclinical Study by Relaxometry at Very Low Magnetic Field

Ruggiero

Itto

Baroni

et al. 2022

Cancers

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“…In a recent study, Feng et al demonstrated that AQP1 knockout (KO) mice exhibited increased growth of glioma cells, which was achieved through the MEK/ERK pathway. The use of MEK inhibitors significantly suppressed tumor growth (Hu et al 2020 ). In this study, we observed that overexpression of AQP1 resulted in the inhibition of proliferation in WT cells.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of aquaporin-1 plays a vital role in proliferation, apoptosis, and pyroptosis of Wilms’ tumor cells

Liu,

Jin,

Xia

et al. 2024

J Cancer Res Clin Oncol

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Background Nephroblastoma, also known as Wilms’ tumor (WT), is an embryonic malignant tumor and one of the most common malignant tumors in the abdominal region of children. The exact role and underlying mechanisms of aquaporin-1 (AQP1) in the occurrence and development of nephroblastoma remain unclear. Methods After overexpression of AQP1, cell proliferation was assessed using the CCK-8 proliferation assay and EdU staining. Flow cytometry was employed to assess cell apoptosis, and Western blotting (WB) analysis was conducted to validate the expression of relevant protein markers. mRNA sequencing (mRNA-Seq) was performed on WT cells overexpressing AQP1 to predict and characterize the associated mechanisms. Transmission electron microscopy was utilized to observe changes in the ultrastructure of WT cells undergoing apoptosis and pyroptosis following AQP1 overexpression. Functional in vivo validation was conducted through animal experiments. Results We validated that overexpression of AQP1 inhibited cell proliferation and promoted cell apoptosis and pyroptosis both in vitro and in vivo. mRNA-Seq analysis of WT cells with AQP1 overexpression suggested that these effects might be mediated through the inhibition of the JAK-STAT signaling pathway. Additionally, we discovered that overexpression of AQP1 activated the classical pyroptosis signaling pathway dependent on caspase-1, thereby promoting pyroptosis in WT. Conclusion These findings highlight the important functional role of AQP1 in the pathobiology of nephroblastoma, providing novel insights into the development of this disease. Moreover, these results offer new perspectives on the potential therapeutic targeting of AQP1 as a treatment strategy for nephroblastoma.

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“…Treatment with the MEK kinase inhibitor trametinib reduced significantly the production of TNF-α by microglia and macrophages in response to HSV treatment and also improved the survival of glioma murine models [ 52 ]. GL261 cells secreted factors, which reduced microglial AQP1 expression via the MEK/ERK pathway, resulting in increased cell migratory activity and reduced TLR4-dependent innate immune response [ 53 ]. The Class A scavenger family member, Macrophage receptor with collagenous structure (MARCO), has been shown to bind to various ligands, such as crystalline silica, oxidized LDL, bacterial lipopolysaccharides and nucleic acids, which are also recognized by TLRs, thus being implicated in the inflammatory response.…”

Section: Targeting Options Of Tams Activitymentioning

confidence: 99%

Targeting Options of Tumor-Associated Macrophages (TAM) Activity in Gliomas

Anagnostakis

Piperi

2023

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Tumor-associated macrophages (TAMs), the most plastic cells of the hematopoietic system exhibit increased tumor infiltrating properties and functional heterogeneity depending on tumor type and associated microenvironment. TAMs constitute a major cell type of cancer-related inflammation, commonly enhancing tumor growth. They are profoundly involved in glioma pathogenesis contributing to many cancer hallmarks such as angiogenesis, survival, metastasis, and immunosuppression. Efficient targeting of TAMs presents a promising approach to tackle glioma progression. Several targeting options involve chemokine signaling axes inhibitors and antibodies, anti-angiogenic factors, immunomodulatory molecules, surface immunoglobulins blockers, receptor and transcription factor inhibitors, as well as microRNAs (miRNAs), administered either as standalones or in combination with other conventional therapies. Herein, we provide a critical overview of current therapeutic approaches targeting TAMs in gliomas with promising outcome.

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Down-regulation of Aquaporin-1 mediates a microglial phenotype switch affecting glioma growth

Cited by 8 publications

References 34 publications

Role of Transmembrane Water Exchange in Glioma Invasion/Migration: In Vivo Preclinical Study by Relaxometry at Very Low Magnetic Field

Role of Transmembrane Water Exchange in Glioma Invasion/Migration: In Vivo Preclinical Study by Relaxometry at Very Low Magnetic Field

Overexpression of aquaporin-1 plays a vital role in proliferation, apoptosis, and pyroptosis of Wilms’ tumor cells

Targeting Options of Tumor-Associated Macrophages (TAM) Activity in Gliomas

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