Brain Cancer-Activated Microglia: A Potential Role for Sphingolipids

Bottai, Daniele; Adami, Raffaella; Paroni, Rita; Ghidoni, Riccardo

doi:10.2174/0929867326666190506120213

Cited by 5 publications

(4 citation statements)

References 168 publications

(185 reference statements)

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“…[38] Various molecules of this pathway play roles ranging from activation to suppression in the pathogenesis of glioblastoma. [39] In our study, phytosphingosine has been demonstrated to induce the autophagy of glioma. [40] Ceramide and sphingomyelin can promote apoptosis of glioma, [41,42] while galabiosylceramide has the potential to participate in killing glioma cells by dendritic and natural killer cells.…”

Section: Discussionmentioning

confidence: 70%

Comprehensive metabolomics study on the pathogenesis of anaplastic astrocytoma via UPLC-Q/TOF-MS

Du¹,

Huang²,

Wei³

et al. 2022

Medicine

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Anaplastic astrocytoma (AA) is a malignant carcinoma whose pathogenesis remains to be fully elucidated. System biology techniques have been widely used to clarify the mechanism of diseases from a systematic perspective.The present study aimed to explore the pathogenesis and novel potential biomarkers for the diagnosis of AA according to metabolic differences. Patients with AA (n = 12) and healthy controls (n = 15) were recruited. Serum was assayed with untargeted ultraperformance liquid chromatography-quadrupole/time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) metabolomic techniques. The data were further evaluated using multivariate analysis and bioinformatic methods based on the KEGG database to determine the distinct metabolites and perturbed pathways.Principal component analysis and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) identified the significance of the distinct metabolic pattern between patients with AA and healthy controls (P < .001) in both ESI modes. Permutation testing confirmed the validity of the OPLS-DA model (permutation = 200, Q2 < 0.5). In total, 24 differentiated metabolites and 5 metabolic pathways, including sphingolipid, glycerophospholipid, caffeine, linoleic acid, and porphyrin metabolism, were identified based on the OPLS-DA model. 3-Methylxanthine, sphinganine, LysoPC(18:1), and lactosylceramide were recognized as potential biomarkers with excellent sensitivity and specificity (area under the curve > 98%).These findings indicate that the perturbed metabolic pattern related to immune regulation and cellular signal transduction is associated with the pathogenesis of AA. 3-Methylxanthine, sphinganine, LysoPC(18:1), and lactosylceramide could be used as biomarkers of AA in future clinical practice. This study provides a therapeutic basis for further studies on the mechanism and precise clinical diagnosis of AA. Abbreviations: AA = anaplastic astrocytoma, ALALA = α-linolenic acid and linoleic acid, AUC = area under the curve, DOS = degradation of superoxide, ESI = electrospray Ionization, HC = healthy Control, HMDB = human metabolites database, IDH = isocitrate dehydrogenase, KEGG = Kyoto Encyclopedia of Genes and Genomes, METC = mitochondrial electron transport chain, MGMT = methylguanine-DNA methyltransferase, MT = mutant type, NOS = not otherwise specified, OPLS-DA = orthogonal projections to latent structures-discriminant analysis, PC = phosphocholine, PCA = principal component analysis, PE = phosphoethanolamine, QC = quality control, THS = thyroid hormone synthesis, UPLC-Q/TOF-MS = liquid chromatography-quadrupole/time-of-flight-mass spectrometry, WT = wide type.

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Section: Discussionmentioning

confidence: 70%

Comprehensive metabolomics study on the pathogenesis of anaplastic astrocytoma via UPLC-Q/TOF-MS

Du¹,

Huang²,

Wei³

et al. 2022

Medicine

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“…Sphingolipids are structural compounds of biological membranes, and recent studies suggest sphingolipids can also serve as secondary messengers, participating in apoptosis, proliferation, senescence, angiogenesis, and vesicular trafficking [39,40]. Because alterations in bioactive sphingolipids have been linked to cancer progression and prognosis, their key metabolic enzymes have been actively pursued as novel targets in cancer drug development [41][42][43][44]. The enrichment analysis showed that SPTSSA is related to the oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

SPTSSA Is a Prognostic Marker for Glioblastoma Associated with Tumor-Infiltrating Immune Cells and Oxidative Stress

Wang

Shi

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. SPTSSA encodes the small subunit A of serine palmitoyltransferase. It catalyzes the formation of sphingoid long-chain base backbone of sphingolipids. Its role in glioma prognosis and tumor-infiltrating immune cells remains unclear. Methods. We analyzed SPTSSA expression and association with clinical prognosis using GEPIA and CGGA database. Then, GSEA was performed to identify relevant biological functions of SPTSSA. The correlations between SPTSSA expression and tumor immune infiltrates were investigated using CIBERSORT and TIMER. Finally, IHC and IF were performed to confirm the value of prognosis and the correlation with immune infiltration. Results. SPTSSA expression was significantly upregulated in diffuse glioma compared to normal tissues and associated with poor survival in GEPIA and CGGA database. Then, we identified biological processes and signaling pathways associated with SPTSSA expression. The result showed that SPTSSA enriched in the GO term like oxidative stress. Finally, we showed that SPTSSA expression was significantly associated with tumor-infiltrating immune cells and overall survival via IHC. Conclusion. These findings suggest that SPTSSA expression might be used as a prognostic biomarker for glioma and potential target for novel glioma therapy.

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“…Acting as a "double-edged sword," microglia play a pivotal role in maintaining tissue homeostasis while partially promoting neurological disease development when exposed to external and internal insults (36,48,49). A release of diverse nucleotides accompanies nerve injury, and some of these nucleotides act as "find/eat-me" signals in mediating neuron-glial interplay (46).…”

Section: Microglia and Neurons Coordinate Cns Homeostasismentioning

confidence: 99%

The crosstalk between parenchymal cells and macrophages: A keeper of tissue homeostasis

Chen

2022

Front. Immunol.

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Non-parenchymal cells (NPCs) and parenchymal cells (PCs) collectively perform tissue-specific functions. PCs play significant roles and continuously adjust the intrinsic functions and metabolism of organs. Tissue-resident macrophages (TRMs) are crucial members of native NPCs in tissues and are essential for immune defense, tissue repair and development, and homeostasis maintenance. As a plastic-phenotypic and prevalent cluster of NPCs, TRMs dynamically assist PCs in functioning by producing cytokines, inflammatory and anti-inflammatory signals, growth factors, and proteolytic enzymes. Furthermore, the PCs of tissues modulate the functional activity and polarization of TRMs. Dysregulation of the PC‐TRM crosstalk axis profoundly impacts many essential physiological functions, including synaptogenesis, gastrointestinal motility and secretion, cardiac pulsation, gas exchange, blood filtration, and metabolic homeostasis. This review focuses on the PC‐TRM crosstalk in mammalian vital tissues, along with their interactions with tissue homeostasis maintenance and disorders. Thus, this review highlights the fundamental biological significance of the regulatory network of PC‐TRM in tissue homeostasis.

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Brain Cancer-Activated Microglia: A Potential Role for Sphingolipids

Cited by 5 publications

References 168 publications

Comprehensive metabolomics study on the pathogenesis of anaplastic astrocytoma via UPLC-Q/TOF-MS

Comprehensive metabolomics study on the pathogenesis of anaplastic astrocytoma via UPLC-Q/TOF-MS

SPTSSA Is a Prognostic Marker for Glioblastoma Associated with Tumor-Infiltrating Immune Cells and Oxidative Stress

The crosstalk between parenchymal cells and macrophages: A keeper of tissue homeostasis

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