Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage

Kou, Yongjun; Geng, Feng; Guo, Deliang

doi:10.3390/biomedicines10081943

Cited by 34 publications

(30 citation statements)

References 269 publications

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“…However, this is a vast oversimplification of these pathways, and a more detailed review of SREBP-1 and FAS in GBM can be found in refs. 32 and 33 .…”

Section: The Four Categories Of Fa Metabolism In Gbmmentioning

confidence: 99%

Targeting fatty acid metabolism in glioblastoma

Miska¹,

Chandel²

2023

Journal of Clinical Investigation

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Glioblastoma (GBM) is a primary tumor of the brain defined by its uniform lethality and resistance to conventional therapies. There have been considerable efforts to untangle the metabolic underpinnings of this disease to find novel therapeutic avenues for treatment. An emerging focus in this field is fatty acid (FA) metabolism, which is critical for numerous diverse biological processes involved in GBM pathogenesis. These processes can be classified into four broad fates: anabolism, catabolism, regulation of ferroptosis, and the generation of signaling molecules. Each fate provides a unique perspective by which we can inspect GBM biology and gives us a road map to understanding this complicated field. This Review discusses the basic, translational, and clinical insights into each of these fates to provide a contemporary understanding of FA biology in GBM. It is clear, based on the literature, that there are far more questions than answers in the field of FA metabolism in GBM, and substantial efforts should be made to untangle these complex processes in this intractable disease.

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“…However, this is a vast oversimplification of these pathways, and a more detailed review of SREBP-1 and FAS in GBM can be found in refs. 32 and 33 .…”

Section: The Four Categories Of Fa Metabolism In Gbmmentioning

confidence: 99%

Targeting fatty acid metabolism in glioblastoma

Miska¹,

Chandel²

2023

Journal of Clinical Investigation

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“…In tumor cells, with the help of ACAT‐1, the cells convert cholesterol to cholesteryl esters and store it in lipid droplets to avoid cytotoxicity induced by high cytoplasm cholesterol level. [ 31 ] It has been shown AVA inhibited tumor proliferation without obvious cytotoxicity to normal cells. [ 32 ] As expected, with EALP treatment, the intracellular cholesterol level was elevated while the content of plasma membrane cholesterol was decreased in B16‐F10 cells as observed by CLSM examination (Figure 3h).…”

Section: Resultsmentioning

confidence: 99%

Blocking Cholesterol Metabolism with Tumor‐Penetrable Nanovesicles to Improve Photodynamic Cancer Immunotherapy

et al. 2022

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Photodynamic therapy (PDT)‐mediated cancer immunotherapy is attenuated due to the dysfunction of T cells in immunosuppressive tumor microenvironment (TME). Cholesterol metabolism plays a vital role in T cell signaling and effector. While the metabolic fitness of tumor infiltrating CD8+ T cells is impaired by nutrition restriction in TME and accumulated metabolites by tumor cells. Here a matrix metalloproteinase‐2‐sensitive tumor‐penetrable nanovesicle is designed to regulate cholesterol metabolism pathway for enhancing photodynamic cancer immunotherapy. The nanovesicles accumulate in tumor and release internalizing RGD to promote deep penetration. Released avasimibe from the nanovesicles simultaneously blocks cholesterol metabolism in CD8+ T and tumor cells, thus reinvigorating the functions of T cells and suppressing the migration of tumor cells. Immune responses induced by PDT‐triggered immunogenic cell death are further improved with cholesterol metabolism blockage. Compared with PDT alone, the designed nanovesicles display enhanced tumor growth inhibition in B16‐F10 mouse tumor model. The approach provides an alternative strategy to improve photodynamic cancer immunotherapy by cholesterol metabolism intervention.

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“…Our ndings are in line with previously published data suggesting lipid metabolic alterations in GBM. [22] In addition, mannitol was upregulated in recurrent tissue compared to the original tumor, suggesting BBB permeability changes after surgical resection and chemoradiation. This may suggest mannitol as a vehicle to guide targeted treatment.…”

Section: Discussionmentioning

confidence: 99%

A pilot study on metabolomic characterization of human glioblastomas and patient plasma

Liu

Aboud

Dahabiyeh

et al. 2023

Preprint

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Purpose To determine whether recurrent GBMs are metabolically distinct from primary GBM, and whether patient plasma can be used as a liquid biopsy to reflect this difference. Methods In a single center cohort study, tissue and blood samples from 15 patients with glioblastoma (9 glioblastoma tissues at diagnosis, 3 pairs of tissue, and 6 pairs of plasma specimens at diagnosis and at recurrence) were analyzed. Results Several metabolites had significant alternations in both tumor and plasma specimens. In the tissue, the following representative metabolites had a significant increase in peak intensity at recurrence compared to diagnosis: N-alpha-methylhistamine (p = 0.037), glycerol-3-phosphate (p = 0.029), phosphocholine (p = 0.045), and succinic acid (p = 0.025). In patient plasma, metabolites that significantly increased at recurrence included: 2,4-difluorotoluene (p = 0.031), diatrizoic acid (p = 0.032), indole-3-acetate with (p = 0.029), urea (P = 0.025), pseudouridine (p = 0.042), and maltose (p = 0.035). Metabolites that significantly decreased in plasma at recurrence were: eicosenoic acid (p = 0.017), glucose-1-phosphate (p = 0.017), FA 18:2 (linoleic acid) (p = 0.017), arginine (p = 0.036), fatty acids 20:3 (homo-gamma-linolenic acid (p = 0.036), galactosamine (p = 0.007), and FA 18:3 (linolenic acid) (P = 0.012). Principal component analysis showed that the metabolomic profiles differ between tumor tissue and patient plasma. Conclusions Our data suggest that metabolomic profiles of human GBM tissue and patient plasma differ at diagnosis and at recurrence. Many metabolites involved in tumorigenesis and metabolomic flexibility were identified. A larger study using targeted metabolomic assay is warranted to measure the levels of these metabolites, which will help identify the metabolomic signatures in both GBM tissue and patient plasma for risk stratification, clinical outcome prediction, and development of new adjuvant metabolomic-targeting therapy.

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Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage

Cited by 34 publications

References 269 publications

Targeting fatty acid metabolism in glioblastoma

Targeting fatty acid metabolism in glioblastoma

Blocking Cholesterol Metabolism with Tumor‐Penetrable Nanovesicles to Improve Photodynamic Cancer Immunotherapy

A pilot study on metabolomic characterization of human glioblastomas and patient plasma

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