An assay for quantitative analysis of polysialic acid expression in cancer cells

Guo, Xinwen; Elkashef, Sara M.; Patel, Anjana; Morais, Goreti Ribeiro; Shnyder, Steven D.; Loadman, Paul M.; Patterson, Laurence H.; Falconer, Robert A.

doi:10.1016/j.carbpol.2021.117741

Cited by 6 publications

(3 citation statements)

References 20 publications

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“…The detection of PSA on the E. coli surface [ 88 ] and microplate [ 92 ] was thus reported. PSA on cells can also be detected by hydrolyzing Sia residues to generate soluble monomers, which are then quantified by attaching 1,2-diamino-4,5-methyleneoxybenzene (DMB) to the α ketocarboxylic acid at the reducing end [ 111 ]. However, this method necessarily destroys the target glycan and the detection of the reaction product requires HPLC analysis, which is difficult to scale.…”

Section: Manipulating Sialyltransferases At a Molecular Levelmentioning

confidence: 99%

Cellular and Molecular Engineering of Glycan Sialylation in Heterologous Systems

2021

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Glycans have been shown to play a key role in many biological processes, such as signal transduction, immunogenicity, and disease progression. Among the various glycosylation modifications found on cell surfaces and in biomolecules, sialylation is especially important, because sialic acids are typically found at the terminus of glycans and have unique negatively charged moieties associated with cellular and molecular interactions. Sialic acids are also crucial for glycosylated biopharmaceutics, where they promote stability and activity. In this regard, heterogenous sialylation may produce variability in efficacy and limit therapeutic applications. Homogenous sialylation may be achieved through cellular and molecular engineering, both of which have gained traction in recent years. In this paper, we describe the engineering of intracellular glycosylation pathways through targeted disruption and the introduction of carbohydrate active enzyme genes. The focus of this review is on sialic acid-related genes and efforts to achieve homogenous, humanlike sialylation in model hosts. We also discuss the molecular engineering of sialyltransferases and their application in chemoenzymatic sialylation and sialic acid visualization on cell surfaces. The integration of these complementary engineering strategies will be useful for glycoscience to explore the biological significance of sialic acids on cell surfaces as well as the future development of advanced biopharmaceuticals.

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Section: Manipulating Sialyltransferases At a Molecular Levelmentioning

confidence: 99%

Cellular and Molecular Engineering of Glycan Sialylation in Heterologous Systems

2021

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“…Peptides and small organic compounds that were identified as structural and functional mimetics of PSA improved functional recovery after neurotrauma [ 11 , 12 , 13 , 14 ]. PSA is also overexpressed in various tumors, and its expression enhances tumor cell migration and invasion [ 15 , 16 , 17 , 18 ]. In addition, PSA is expressed in the immune system and plays an important role in its innate and adaptive responses [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Small Organic Compounds Mimicking the Effector Domain of Myristoylated Alanine-Rich C-Kinase Substrate Stimulate Female-Specific Neurite Outgrowth

Tschang,

Kumar,

Young

et al. 2023

IJMS

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Myristoylated alanine-rich C-kinase substrate (MARCKS) is a critical member of a signaling cascade that influences disease-relevant neural functions such as neural growth and plasticity. The effector domain (ED) of MARCKS interacts with the extracellular glycan polysialic acid (PSA) through the cell membrane to stimulate neurite outgrowth in cell culture. We have shown that a synthetic ED peptide improves functional recovery after spinal cord injury in female but not male mice. However, peptides themselves are unstable in therapeutic applications, so we investigated more pharmacologically relevant small organic compounds that mimic the ED peptide to maximize therapeutic potential. Using competition ELISAs, we screened small organic compound libraries to identify molecules that structurally and functionally mimic the ED peptide of MARCKS. Since we had shown sex-specific effects of MARCKS on spinal cord injury recovery, we assayed neuronal viability as well as neurite outgrowth from cultured cerebellar granule cells of female and male mice separately. We found that epigallocatechin, amiodarone, sertraline, tegaserod, and nonyloxytryptamine bind to a monoclonal antibody against the ED peptide, and compounds stimulate neurite outgrowth in cultured cerebellar granule cells of female mice only. Therefore, a search for compounds that act in males appears warranted.

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“…Sialyl Lewis x, sialyl Lewis a, sialyl Tn, and polysialic acid are well-studied and common carbohydrate tumor markers for the diagnosis, prognosis, and prediction of cancer [ 6 , 7 , 8 , 9 , 10 ]. Moreover, disialic, oligosialic, and polysialic acids can be obtained by the addition of sialic acids via α2,8-linkage [ 11 ]. α2,8-linkage sialylation is catalyzed by six membranes of the α2,8 sialyltransferases (ST8SIA) family, which has been correlated with clinical outcomes [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics Analyses Identify the Therapeutic Potential of ST8SIA6 for Colon Cancer

Chu

Hsu

et al. 2022

JPM

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Sialylation of glycoproteins is modified by distinct sialyltransferases such as ST3Gal, ST6Gal, ST6GalNAc, or ST8SIA with α2,3-, α2,6-, or α2,8-linkages. Alteration of these sialyltransferases causing aberrant sialylation is associated with the progression of colon cancer. However, among the ST8- sialyltransferases, the role of ST8SIA6 in colon cancer remains poorly understood. In this study, we explored the involvement of ST8SIA6 in colon cancer using multiple gene databases. The relationship between ST8SIA6 expression and tumor stages/grades was investigated by UALCAN analysis, and Kaplan–Meier Plotter analysis was used to analyze the expression of ST8SIA6 on the survival outcome of colon cancer patients. Moreover, the biological functions of ST8SIA6 in colon cancer were explored using LinkedOmics and cancer cell metabolism gene DB. Finally, TIMER and TISMO analyses were used to delineate ST8SIA6 levels in tumor immunity and immunotherapy responses, respectively. ST8SIA6 downregulation was associated with an advanced stage and poorly differentiated grade; however, ST8SIA6 expression did not affect the survival outcomes in patients with colon cancer. Gene ontology analysis suggested that ST8SIA6 participates in cell surface adhesion, angiogenesis, and membrane vesicle trafficking. In addition, ST8SIA6 levels affected immunocyte infiltration and immunotherapy responses in colon cancer. Collectively, these results suggest that ST8SIA6 may serve as a novel therapeutic target towards personalized medicine for colon cancer.

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An assay for quantitative analysis of polysialic acid expression in cancer cells

Cited by 6 publications

References 20 publications

Cellular and Molecular Engineering of Glycan Sialylation in Heterologous Systems

Cellular and Molecular Engineering of Glycan Sialylation in Heterologous Systems

Small Organic Compounds Mimicking the Effector Domain of Myristoylated Alanine-Rich C-Kinase Substrate Stimulate Female-Specific Neurite Outgrowth

Bioinformatics Analyses Identify the Therapeutic Potential of ST8SIA6 for Colon Cancer

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