Glioma cells are resistant to inflammation‑induced alterations of mitochondrial dynamics

Fan, Wange; Song, Yanan; Ren, Zongyao; Cheng, Xiaoli; Li, Pu; Song, Haiyan; Jia, Ling

doi:10.3892/ijo.2020.5134

Cited by 18 publications

(17 citation statements)

References 63 publications

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“…β2 microglobulin and cytochrome C oxidase subunit 6B1 showed a similar trend and significantly higher levels of m-GBM, again confirming differences between male and female GBM profiles. These results are in accordance with the reported overexpression of cytochrome C oxidase subunit 6B1 in gliomas, which accomplishes mitochondrial metabolic remodeling in this disease, and it is involved in apoptosis inhibition, mitochondrial function modulation, and stress resistance [ 22 ].…”

Section: Resultssupporting

confidence: 91%

Pediatric Brain Tumors: Signatures from the Intact Proteome

Rossetti

Inserra

Nesticò

et al. 2022

IJMS

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The present investigation aimed to explore the intact proteome of tissues of pediatric brain tumors of different WHO grades and localizations, including medulloblastoma, pilocytic astrocytoma, and glioblastoma, in comparison with the available data on ependymoma, to contribute to the understanding of the molecular mechanisms underlying the onset and progression of these pathologies. Tissues have been homogenized in acidic water–acetonitrile solutions containing proteases inhibitors and analyzed by LC–high resolution MS for proteomic characterization and label-free relative quantitation. Tandem MS spectra have been analyzed by either manual inspection or software elaboration, followed by experimental/theoretical MS fragmentation data comparison by bioinformatic tools. Statistically significant differences in protein/peptide levels between the different tumor histotypes have been evaluated by ANOVA test and Tukey’s post-hoc test, considering a p-value > 0.05 as significant. Together with intact protein and peptide chains, in the range of molecular mass of 1.3–22.8 kDa, several naturally occurring fragments from major proteins, peptides, and proteoforms have been also identified, some exhibiting proper biological activities. Protein and peptide sequencing allowed for the identification of different post-translational modifications, with acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations being the most frequently characterized. C-terminal truncations, lacking from two to four amino acid residues, particularly characterizing the β-thymosin peptides and ubiquitin, showed a different modulation in the diverse tumors studied. With respect to the other tumors, medulloblastoma, the most frequent malignant brain tumor of the pediatric age, was characterized by higher levels of thymosin β4 and β10 peptides, the latter and its des-IS form particularly marking this histotype. The distribution pattern of the C-terminal truncated forms was also different in glioblastoma, particularly underlying gender differences, according to the definition of male and female glioblastoma as biologically distinct diseases. Glioblastoma was also distinguished for the peculiar identification of the truncated form of the α-hemoglobin chain, lacking the C-terminal arginine, and exhibiting oxygen-binding and vasoconstrictive properties different from the intact form. The proteomic characterization of the undigested proteome, following the top-down approach, was challenging to originally investigate the post-translational events that differently characterize pediatric brain tumors. This study provides a contribution to elucidate the molecular profiles of the solid tumors most frequently affecting the pediatric age, and which are characterized by different grades of aggressiveness and localization.

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Section: Resultssupporting

confidence: 91%

Pediatric Brain Tumors: Signatures from the Intact Proteome

Rossetti

Inserra

Nesticò

et al. 2022

IJMS

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“…The analysis revealed that T98G cells showed increased basal levels of ROS, which did not change after menadione treatment, whereas HepG2 cells responded to the treatment and OS was induced (Figure 1C). This might indicate that the redox state of GBM cells protects them from apoptosis, thus creating a favorable environment for cellular proliferation and inducing drug resistance [10,57].…”

Section: Discussionmentioning

confidence: 99%

Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives

et al. 2021

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Recently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by interfering with the redox status of cancer cells. Thus, these compounds might serve as potential alternatives in the oxidative therapy of GBM. The increased basal levels of reactive oxygen species (ROS) in GBM support the survival of cancer cells and cause drug resistance. The simplest approach to induce cell death is to achieve the redox threshold and circumvent the antioxidant defense mechanisms. Consequently, cells become more sensitive to oxidative stress (OS) caused by exogenous agents. Here, we investigated the effect of KR and its derivatives on the redox status of T98G cells in 2D and 3D cell culture. The use of spheroids of T98G cells enabled the selection of one derivative—7-deazaKR—with comparable antitumor activity to KR. Both compounds induced ROS generation and genotoxic OS, resulting in lipid peroxidation and leading to apoptosis. Taken together, these results demonstrated that KR and 7-deazaKR modulate the cellular redox environment of T98G cells, and vulnerability of these cells is dependent on their antioxidant capacity.

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“…Glioblastoma is known to foster an inflammatory immune response that could shift the tumor microenvironment into a pro-tumorigenic milieu ( Fan et al, 2020 ). Acute and transient inflammation may inhibit tumor growth ( Fan et al, 2020 ) by upregulating pro-inflammatory cytokines such as TNFα, IL-1β, and IL-6 that are part of the initial inflammatory cascade and recruit other downstream targets to enhance anti-tumor responses. However, if inflammation becomes a chronic occurrence, the same inflammatory processes can exhaust the immune system’s ability to fend off glioma cells.…”

Section: Inflammation In Gliomamentioning

confidence: 99%

Role of RAGE and Its Ligands on Inflammatory Responses to Brain Tumors

Otazu

Dayyani

Badie

2021

Front. Cell. Neurosci.

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Gliomas, the most common form of brain cancer, can range from relatively slow-growing low-grade to highly aggressive glioblastoma that has a median overall survival of only 15 months despite multimodal standard therapy. Although immunotherapy with checkpoint inhibitors has significantly improved patient survival for some cancers, to date, these agents have not shown consistent efficacy against malignant gliomas. Therefore, there is a pressing need to better understand the impact of host inflammatory responses on the efficacy of emerging immunotherapy approaches for these resistant tumors. RAGE is a multi-ligand pattern recognition receptor that is activated in various inflammatory states such as diabetes, Alzheimer’s disease, cystic fibrosis, and cancer. Low levels of RAGE can be found under normal physiological conditions in neurons, immune cells, activated endothelial, and vascular smooth muscle cells, but it is over-expressed under chronic inflammation due to the accumulation of its ligands. RAGE binds to a range of damage-associated molecular pattern molecules (DAMPs) including AGEs, HMGB1, S100s, and DNA which mediate downstream cellular responses that promote tumor growth, angiogenesis, and invasion. Both in vitro and in vivo studies have shown that inhibition of RAGE signaling can disrupt inflammation and cancer progression and metastasis. Here, we will review our current understanding of the role of RAGE pathway on glioma progression and how it could be exploited to improve the efficacy of immunotherapy approaches.

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Glioma cells are resistant to inflammation‑induced alterations of mitochondrial dynamics

Cited by 18 publications

References 63 publications

Pediatric Brain Tumors: Signatures from the Intact Proteome

Pediatric Brain Tumors: Signatures from the Intact Proteome

Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives

Role of RAGE and Its Ligands on Inflammatory Responses to Brain Tumors

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