Autophagy: A strategy for malignant gliomas’ resistance to therapy

Ge, Pengfei; Luo, Yan; Fu, Shuanglin; Ji, Xunmin; Li, Feng

doi:10.1016/j.mehy.2008.11.047

Cited by 6 publications

(2 citation statements)

References 30 publications

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“…However, the complex interplay between autophagy and apoptosis machinery is still controversial and not fully clarified [36]. In particular, the prognosis of GBM could be influenced by autophagy, either positively [37,38] or negatively [39,40,41,42], as well as a defective autophagic pathway has been associated with GBM [43]. Of note, autophagy may limit the tumor-associated inflammation profile through the removal of inflammasomes as well as damaged mitochondria, which are considered to be crucial in supporting the inflammatory microenvironment determinant for tumor progression and invasiveness [44].…”

Section: Discussionmentioning

confidence: 99%

NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line

Palumbo

Lombardi

Augello

et al. 2019

IJMS

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The relevance of nitric oxide synthase 2 (NOS2) as a prognostic factor in Glioblastoma Multiforme (GBM) malignancy is emerging. We analyzed the effect of NOS2 inhibitor 1400W on the autophagic flux and extracellular vesicle (EV) secretion in U87MG glioma cells. The effects of glioma stem cells (GSC)-derived EVs on adherent U87MG were evaluated. Cell proliferation and migration were examined while using Cell Counting Kit-8 assay (CCK-8) and scratch wound healing assay. Cell cycle profile and apoptosis were analyzed by flow cytometry. Autophagy-associated acidic vesicular organelles were detected and quantified by acridine orange staining. The number and size of EVs were assessed by nanoparticle tracking analysis. EV ultrastructure was verified by transmission electron microscopy (TEM). WB was used to analyze protein expression and acid sphingomyelinase was determined through ceramide levels. 1400W induced autophagy and EV secretion in both adherent U87MG and GSCs. EVs secreted by 1400W-treated GSC, but not those from untreated cells, were able to inhibit adherent U87MG cell growth and migration while also inducing a relevant level of autophagy. The hypothesis of NOS2 expression as GBM profile marker or interesting therapeutic target is supported by our findings. Autophagy and EV release following treatment with the NOS2 inhibitor could represent useful elements to better understand the complex biomolecular frame of GBM.

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Section: Discussionmentioning

confidence: 99%

NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line

Palumbo

Lombardi

Augello

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…Oncolytic adenoviral vectors induce autophagy in malignant glioblastoma cells (227,228). Autophagic tumor cells are not necessarily so due to fusion with a macrophage (204)(205)(206): autophagy may be a sign of viral infection, attack by cytotoxic lymphocytes (49), or a survival strategy of a chemotherapy-damaged tumor cell (229).…”

Section: Fusogenic Viruses Malignant Murine T Lymphoma Cells Gained mentioning

confidence: 99%

Horizontal gene transfers and cell fusions in microbiology, immunology and oncology (Review)

Sinkovics¹

2009

Int J Oncol

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High LC3/Beclin Expression Correlates with Poor Survival in Glioma: a Definitive Role for Autophagy as Evidenced by In Vitro Autophagic Flux

Vijayakurup

et al. 2017

Pathol. Oncol. Res.

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Recent studies suggest the role of autophagy, an evolutionarily conserved catabolic process, in determining the response of gliomas to treatment either positively or negatively. The study attempts to characterize autophagy in low and high-grade glioma by investigating the autophagic flux and clinical significance of autophagy proteins (LC3 and beclin 1) in a group of glioma patients. We evaluated the expression of autophagic markers in resected specimens of low-grade glioma (LGG) and high-grade glioma (HGG) tissues, by immunohistochemistry and Western blotting. Our results show that expression of autophagy proteins were more prominent in HGG than in LGG. Increased level of autophagic proteins in HGG can be due to an increased rate of autophagy or can be because of blockage in the final degradation step of autophagy (defective autophagy). To distinguish these possibilities, the autophagic flux assay which helps to determine the rate of degradation/synthesis of autophagic proteins (LC3-II and p62) over a period of time by blocking the final degradation step of autophagy using bafilomycin A1 was used . The assessment of autophagic flux in ex vivo culture of primary glioma cells revealed for the first time increased turnover of autophagy in high grade compared to low grade-glioma. Though autophagic markers were reduced in LGG, functionally autophagy was non defective in both grades of glioma. We then investigated whether autophagy in gliomas is regulated by nutrient sensing pathways including mTOR and promote cell survival by providing an alternate energy source in response to metabolic stress. The results depicted that the role of autophagy during stress varies with tissue and has a negative correlation with mTOR substrate phosphorylation. We also evaluated the expression of LC3 and beclin 1 with progression free survival (PFS) using Kaplan-Meier survival analysis and have found that patients with low LC3/beclin 1 expression had better PFS than those with high expression of LC3/beclin 1 in their tumors. Together, we provide evidence that autophagy is non-defective in glioma and also show that high LC3/beclin 1 expression correlates with poor PFS in both LGG and HGG.

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Autophagy: A strategy for malignant gliomas’ resistance to therapy

Cited by 6 publications

References 30 publications

NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line

NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line

Horizontal gene transfers and cell fusions in microbiology, immunology and oncology (Review)

High LC3/Beclin Expression Correlates with Poor Survival in Glioma: a Definitive Role for Autophagy as Evidenced by In Vitro Autophagic Flux

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