Altered sphingolipid metabolism induced by tumor hypoxia – New vistas in glycolipid tumor markers

Yin, Jun; Miyazaki, Kohji; Shaner, Rebecca L.; Merrill, Alfred H.; Kannagi, Reiji

doi:10.1016/j.febslet.2009.11.019

Cited by 55 publications

(47 citation statements)

References 43 publications

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“…Such as glycoproteins, glycolipids also change during malignant transformation, and these changes seem to be involved in the molecular mechanisms needed for early and late stages of carcinogenesis [126-128]. These changes are also affected by hypoxia, as demonstrated by Tanaka et al in human colorectal cancer cells (Caco-2) under hypoxic conditions (O 2 1%) for three days [129].…”

Section: Hypoxia Changes Membrane Glycoconjugates In Tumor Cellsmentioning

confidence: 89%

“…Because it is an oxidative hydroxylation, this process, and the concomitant production of NeuGc through de novo synthesis, may be suppressed in hypoxic tissues in mammals that express CMP-NeuAc-hydroxylase. In contrast, the expression of NeuGc increases under hypoxic conditions in humans, where its level is determined by its salvaging through the transporter Sialin, instead of de novo synthesis [128]. …”

Section: Hypoxia Changes Membrane Glycoconjugates In Tumor Cellsmentioning

confidence: 99%

“…Cytidine Monophospho-N-Acetylneuraminic Acid (CMP-NeuAc)-hydroxylase oxidase is present in many mammals, but absent in humans, and is the enzyme responsible for de novo synthesis of N-glycolyl sialic acid through oxidative hydroxylation of N-acetyl sialic acid [128, 132]. Because it is an oxidative hydroxylation, this process, and the concomitant production of NeuGc through de novo synthesis, may be suppressed in hypoxic tissues in mammals that express CMP-NeuAc-hydroxylase.…”

Section: Hypoxia Changes Membrane Glycoconjugates In Tumor Cellsmentioning

confidence: 99%

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Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

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Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

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Section: Hypoxia Changes Membrane Glycoconjugates In Tumor Cellsmentioning

confidence: 89%

Section: Hypoxia Changes Membrane Glycoconjugates In Tumor Cellsmentioning

confidence: 99%

Section: Hypoxia Changes Membrane Glycoconjugates In Tumor Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

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“…Therefore, following the popularity and successful achievements of HPLC-MS in proteomics [68] in the last few years, LC-MS was intensively developed and also introduced for glycolipidomic surveys. This method is currently of routine use in several laboratories for the research related to compositional and structural analysis of various lipid-linked carbohydrates originating in minute amounts from clinical samples [69][70][71].…”

Section: Lc-msmentioning

confidence: 99%

High‐performance separation techniques hyphenated to mass spectrometry for ganglioside analysis

et al. 2011

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Gangliosides, sialic-acid-containing glycosphingolipids are involved in numerous biological processes and play essential roles in severe pathologies, with predilection in those of the central nervous system. Formerly, ganglioside composition and quantity were assessed exclusively by thin-layer chromatographic (TLC), immunochemical, and immunohistochemical methods, which have limited effectiveness being unable to detect minor components in mixtures of high heterogeneity. Increased awareness of the biological importance of gangliosides stimulated the development of analytical methods that are better amenable to complex ganglioside mixtures. More recently, MS in online conjunction with high-performance separation techniques brought a significant progress to the field. This review highlights the state-of-the-art development and application of separation methods online coupled to MS for ganglioside analysis. Most original and successful protocols based on GC-MS, LC-MS, and CE-MS are presented here together with the special instrumental and sample preparation requirements to be met for effective ganglioside separation, detection, and structural identification. Finally, the advantages and downsides of each methodology as well as the perspectives for simplification, standardization, and upgrading are assessed.

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“…Predominance of b-series gangliosides was found in cerebellum, and of a-series gangliosides in hippocampal archicortex and the amygdala [11]. Due to their regional and temporal distribution, gangliosides can serve as neurodevelopmental and aging markers as well as biomarkers for specific pathological processes [4,5,12].…”

Section: Introductionmentioning

confidence: 99%

Role of gangliosides in brain aging and neurodegeneration

Mlinac

Bognar

2010

Translational Neuroscience

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Role of GanGlIosIdes In bRaIn aGInG and neuRodeGeneRatIon abstractGangliosides are membrane glycosphingolipids bearing sialic acid residues. Within membranes, gangliosides are specifically enriched in highly organized domains, lipid rafts, and are attributed with diverse functions such as intercellular interactions, cell recognition, neurotransmission, and signal transduction. The highest concentration and variability of ganglioside structures are found in the human brain. Specific temporal and regional distribution of brain gangliosides has been reported; moreover, gangliosides may serve as markers of neurodevelopmental stages, aging and neurodegeneration. Brain ganglioside content and composition as well as ganglioside metabolism are altered in Alzheimer's disease. It appears that the alterations of ganglioside metabolism leading to changes in membrane physico-chemical properties are not merely a consequence of primary pathology, but may also be involved in the early pathogenesis of Alzheimer's disease through documented effects on APP proteolytic processing and amyloid aggregation. Investigations of glycolipid metabolic alterations which accompany neurodegenerative disorders provide insight into pathogenetic mechanisms and enable recognition of diagnostic markers as well as molecular structures acting as therapeutic tools interfering with cascade of pathological events.

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Altered sphingolipid metabolism induced by tumor hypoxia – New vistas in glycolipid tumor markers

Cited by 55 publications

References 43 publications

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

High‐performance separation techniques hyphenated to mass spectrometry for ganglioside analysis

Role of gangliosides in brain aging and neurodegeneration

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