Stable Isotope Labeling Highlights Enhanced Fatty Acid and Lipid Metabolism in Human Acute Myeloid Leukemia

Stuani, Lucille; Riols, Fabien; Millard, Pierre; Sabatier, Marie; Batut, Aurélie; Saland, Estelle; Viars, Fanny; Tonini, Laure; Zaghdoudi, Sonia; Linares, Laëtitia K.; Portais, Jean‐Charles; Sarry, Jean-Emmanuel; Bertrand‐Michel, Justine

doi:10.3390/ijms19113325

Cited by 47 publications

(48 citation statements)

References 68 publications

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“…Thus, complimentary secretome findings from other stem cell sources will provide a powerful reference for the identification of similar factors within the NSC secretome. Finally, the advent of techniques such as SILAC will help identify NSC-secreted proteins (Prokhorova et al, 2009) and/or lipids (Stuani et al, 2018) in co-culture.…”

Section: Modulation Of Cellular Responses Nsc-secreted Factors and Immentioning

confidence: 99%

Harnessing the Neural Stem Cell Secretome for Regenerative Neuroimmunology

Willis

Nicaise

Hamel

et al. 2020

Front. Cell. Neurosci.

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Increasing evidence foresees the secretome of neural stem cells (NSCs) to confer superimposable beneficial properties as exogenous NSC transplants in experimental treatments of traumas and diseases of the central nervous system (CNS). Naturally produced secretome biologics include membrane-free signaling molecules and extracellular membrane vesicles (EVs) capable of regulating broad functional responses. The development of high-throughput screening pipelines for the identification and validation of NSC secretome targets is still in early development. Encouraging results from pre-clinical animal models of disease have highlighted secretome-based (acellular) therapeutics as providing significant improvements in biochemical and behavioral measurements. Most of these responses are being hypothesized to be the result of modulating and promoting the restoration of key inflammatory and regenerative programs in the CNS. Here, we will review the most recent findings regarding the identification of NSC-secreted factors capable of modulating the immune response to promote the regeneration of the CNS in animal models of CNS trauma and inflammatory disease and discuss the increased interest to refine the pro-regenerative features of the NSC secretome into a clinically available therapy in the emerging field of Regenerative Neuroimmunology.

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Section: Modulation Of Cellular Responses Nsc-secreted Factors and Immentioning

confidence: 99%

Harnessing the Neural Stem Cell Secretome for Regenerative Neuroimmunology

Willis

Nicaise

Hamel

et al. 2020

Front. Cell. Neurosci.

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“…Experiments on acute myeloid leukemia HL60 line have demonstrated that IDH1 mutation causes an increase in lipid anabolic fluxes [98] and significantly more MUFA and more SFA, albeit not statistically significantly (p = 0.07) [98]. In the same experiment, the level of PUFA in the studied cells did not differ between those with or without the IDH mutation (p = 0.6) [98]. The observed changes were confirmed on the glioma tumor with and without the IDH1 mutation.…”

Section: Effect Of Mutation In Idh1/2 Genes On the Expression Of Desamentioning

confidence: 99%

Expression of SCD and FADS2 Is Lower in the Necrotic Core and Growing Tumor Area than in the Peritumoral Area of Glioblastoma Multiforme

et al. 2020

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The expression of desaturases is higher in many types of cancer, and despite their recognized role in oncogenesis, there has been no research on the expression of desaturases in glioblastoma multiforme (GBM). Tumor tissue samples were collected during surgery from 28 patients (16 men and 12 women) diagnosed with GBM. The effect of necrotic conditions and nutritional deficiency (mimicking conditions in the studied tumor zones) was studied in an in vitro culture of human brain (glioblastoma astrocytoma) U-87 MG cells. Analysis of desaturase expression was made by qRT-PCR and the immunohistochemistry method. In the tumor, the expression of stearoyl–coenzyme A desaturase (SCD) and fatty acid desaturases 2 (FADS2) was lower than in the peritumoral area. The expression of other desaturases did not differ in between the distinguished zones. We found no differences in the expression of SCD, fatty acid desaturases 1 (FADS1), or FADS2 between the sexes. Necrotic conditions and nutritional deficiency increased the expression of the studied desaturase in human brain (glioblastoma astrocytoma) U-87 MG cells. The obtained results suggest that (i) biosynthesis of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) in a GBM tumor is less intense than in the peritumoral area; (ii) expressions of SCD, SCD5, FADS1, and FADS2 correlate with each other in the necrotic core, growing tumor area, and peritumoral area; (iii) expressions of desaturases in a GBM tumor do not differ between the sexes; and (iv) nutritional deficiency increases the biosynthesis of MUFA and PUFA in GBM cells.

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“…This makes fatty acids robust biomarker candidates. Recent studies have shown that genetic alterations observed in acute myeloid leukemia (AML) patients control lipid dynamics and metabolism [ 39 , 85 ]. Interestingly, patients with AML can be identified by specific lipid signatures in plasma [ 86 ] and bone marrow [ 87 ].…”

Section: Lipids As Biomarkers Of Immune Response To Cancermentioning

confidence: 99%

Lipidomic-Based Advances in Diagnosis and Modulation of Immune Response to Cancer

Balgoma

Montero

2020

Metabolites

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While immunotherapies for diverse types of cancer are effective in many cases, relapse is still a lingering problem. Like tumor cells, activated immune cells have an anabolic metabolic profile, relying on glycolysis and the increased uptake and synthesis of fatty acids. In contrast, immature antigen-presenting cells, as well as anergic and exhausted T-cells have a catabolic metabolic profile that uses oxidative phosphorylation to provide energy for cellular processes. One goal for enhancing current immunotherapies is to identify metabolic pathways supporting the immune response to tumor antigens. A robust cell expansion and an active modulation via immune checkpoints and cytokine release are required for effective immunity. Lipids, as one of the main components of the cell membrane, are the key regulators of cell signaling and proliferation. Therefore, lipid metabolism reprogramming may impact proliferation and generate dysfunctional immune cells promoting tumor growth. Based on lipid-driven signatures, the discrimination between responsiveness and tolerance to tumor cells will support the development of accurate biomarkers and the identification of potential therapeutic targets. These findings may improve existing immunotherapies and ultimately prevent immune escape in patients for whom existing treatments have failed.

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Stable Isotope Labeling Highlights Enhanced Fatty Acid and Lipid Metabolism in Human Acute Myeloid Leukemia

Cited by 47 publications

References 68 publications

Harnessing the Neural Stem Cell Secretome for Regenerative Neuroimmunology

Harnessing the Neural Stem Cell Secretome for Regenerative Neuroimmunology

Expression of SCD and FADS2 Is Lower in the Necrotic Core and Growing Tumor Area than in the Peritumoral Area of Glioblastoma Multiforme

Lipidomic-Based Advances in Diagnosis and Modulation of Immune Response to Cancer

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