Glycation Leads to Increased Polysialylation and Promotes the Metastatic Potential of Neuroblastoma Cells

Scheer, Maximilian; Bork, Kaya; Simon, Frieder; Nagasundaram, Manimozhi; Horstkorte, Rüdiger; Gnanapragassam, Vinayaga S.

doi:10.3390/cells9040868

Cited by 12 publications

(10 citation statements)

References 35 publications

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“…In our previous study, we demonstrated that glycation with MGO increases the invasion of GBM cells, resulting in a more aggressive subtype [18]. Similar results were found in meningioma and neuroblastoma, where invasion was increased after glycation [19,20]. Interestingly, glycation increased polysialylated neural cell adhesion molecule (PolySia-NCAM) in neuroblastoma cells, where PolySia-NCAM is seen as an adverse prognostic marker [19].…”

Section: Introductionsupporting

confidence: 68%

Glycation Interferes with the Expression of Sialyltransferases and Leads to Increased Polysialylation in Glioblastoma Cells

Schildhauer,

Selke,

Staege

et al. 2023

Cells

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Glioblastoma (GBM) is a highly aggressive brain tumor that often utilizes aerobic glycolysis for energy production (Warburg effect), resulting in increased methylglyoxal (MGO) production. MGO, a reactive dicarbonyl compound, causes protein alterations and cellular dysfunction via glycation. In this study, we investigated the effect of glycation on sialylation, a common post-translational modification implicated in cancer. Our experiments using glioma cell lines, human astrocytes (hA), and primary glioma samples revealed different gene expressions of sialyltransferases among cells, highlighting the complexity of the system. Glycation has a differential effect on sialyltransferase expression, upregulating ST8SIA4 in the LN229 and U251 cell lines and decreasing the expression in normal hA. Subsequently, polysialylation increased in the LN229 and U251 cell lines and decreased in hA. This increase in polysialylation could lead to a more aggressive phenotype due to its involvement in cancer hallmark processes such as immune evasion, resistance to apoptosis, and enhancing invasion. Our findings provide insights into the mechanisms underlying GBM aggressiveness and suggest that targeting glycation and sialylation could be a potential therapeutic strategy.

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Section: Introductionsupporting

confidence: 68%

Glycation Interferes with the Expression of Sialyltransferases and Leads to Increased Polysialylation in Glioblastoma Cells

Schildhauer,

Selke,

Staege

et al. 2023

Cells

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“…The bifunctional effects of SLs in maintaining a proper balance between the neural system health and control of hypersalivation for the life process may play a crucial role. Such balance could avoid the formation of the excessed polySia chains, and thus may block tumor metastasis of cancer patients [59]. As Toman's Law states: "Enough of Anything will Inhibit Anything" [60].…”

Section: Discussionmentioning

confidence: 99%

The NMR Studies of the Interactions between Sialyllactoses and Polysialytransferase Domain for the Polysialylation Inhibition

Lu,

Liao,

Liang

et al. 2024

Preprint

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Sialylated milk oligosaccharides (SMOs) is the most important oligosaccharides in human milk oligosaccharides (HMOs), and have a multifunctional health benefit, and the most abundant SMOs are sialyllactose (SLs). The previous studies indicate that the growth of tumor cells, and angiogenesis on tumor tissues with Lewis lung carcinoma, melanoma, and colon carcinoma cells could be prevented by SL. Thus, it has been proposed that SL might be an ideal candidate for the development of anti-angiogenic drugs without any side effects. It has been proposed that the Sialic acid (Sia) can be produced through SL’s hydrolysis, and the dietary Sia is further transported to the brain and other tissues though blood for formation of CMP-Sia, the activated precursor of Sia, and then is catalyzed by polysialyltransferases (polySTs) for synthesis of polysialic acid (polySia) or polysialylation of neural cell adhesion molecule (NCAM). Thus, it’s necessary to study and develop new inhibitors, which not only modulate a proper balance between the gut health and neuros system development, but also inhibit the overexpression of polySia, and thus block the tumor cell migration. In this study, we proposed that 3’-SL and 6’-SL may be more ideal inhibitors comparing with two previous inhibitors, the low molecular weight heparin (LMWH) and cytidine monophosphate (CMP) in the previous studies.

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“…Polysialic acid is an α-2,8-glycosidically linked polymer of Sia, usually expressed as N -glycans on neural cell adhesion molecule 1 (NCAM1) ( 35 ). The abnormal expression of polysialic acid is associated with the occurrence of lung cancer ( 35 ), breast cancer ( 36 ), and neuroblastoma ( 37 ), and is associated with poor prognosis ( 38 ). The increased level of sialylation also involves overexpression of gangliosides ( 39 – 42 ).…”

Section: Aberrant Glycosylation In Tumorsmentioning

confidence: 99%

Cancer glycomics offers potential biomarkers and therapeutic targets in the framework of 3P medicine

et al. 2022

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Glycosylation is one of the most important post-translational modifications (PTMs) in a protein, and is the most abundant and diverse biopolymer in nature. Glycans are involved in multiple biological processes of cancer initiation and progression, including cell-cell interactions, cell-extracellular matrix interactions, tumor invasion and metastasis, tumor angiogenesis, and immune regulation. As an important biomarker, tumor-associated glycosylation changes have been extensively studied. This article reviews recent advances in glycosylation-based biomarker research, which is useful for cancer diagnosis and prognostic assessment. Truncated O-glycans, sialylation, fucosylation, and complex branched structures have been found to be the most common structural patterns in malignant tumors. In recent years, immunochemical methods, lectin recognition-based methods, mass spectrometry (MS)-related methods, and fluorescence imaging-based in situ methods have greatly promoted the discovery and application potentials of glycomic and glycoprotein biomarkers in various cancers. In particular, MS-based proteomics has significantly facilitated the comprehensive research of extracellular glycoproteins, increasing our understanding of their critical roles in regulating cellular activities. Predictive, preventive and personalized medicine (PPPM; 3P medicine) is an effective approach of early prediction, prevention and personalized treatment for different patients, and it is known as the new direction of medical development in the 21st century and represents the ultimate goal and highest stage of medical development. Glycosylation has been revealed to have new diagnostic, prognostic, and even therapeutic potentials. The purpose of glycosylation analysis and utilization of biology is to make a fundamental change in health care and medical practice, so as to lead medical research and practice into a new era of 3P medicine.

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Glycation Leads to Increased Polysialylation and Promotes the Metastatic Potential of Neuroblastoma Cells

Cited by 12 publications

References 35 publications

Glycation Interferes with the Expression of Sialyltransferases and Leads to Increased Polysialylation in Glioblastoma Cells

Glycation Interferes with the Expression of Sialyltransferases and Leads to Increased Polysialylation in Glioblastoma Cells

The NMR Studies of the Interactions between Sialyllactoses and Polysialytransferase Domain for the Polysialylation Inhibition

Cancer glycomics offers potential biomarkers and therapeutic targets in the framework of 3P medicine

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