The Cancer-Associated Antigens Sialyl Lewisa/x and Sda: Two Opposite Faces of Terminal Glycosylation

Dall’Olio, Fabio; Pucci, Michela; Malagolini, Nadia

doi:10.3390/cancers13215273

Cited by 23 publications

(15 citation statements)

References 95 publications

(131 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These sialic acids are attached in multiple anomeric linkages in glycoproteins, primarily as α2,3 or α2,6 isomers, as well as different types of α2,8 and α2,9 isomers . In human cancers, α2,3-linked sialic acids are associated with common carbohydrate tumor antigens like sialyl Lewis A (CA19-9), sialyl Lewis X, and sTRA, , and increases in α2,6 sialylation have been associated with multiple cancer types. , The roles of α2,3 and α2,6 sialic acids in influenza virus infections are also well documented. , The gangliosides, a class of sialylated glycosphingolipids particularly abundant in brain, are composed of multiple sialylated species attached in α2,3 and α2,8 linkages …”

Section: Introductionmentioning

confidence: 99%

Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids

McDowell

Blaschke

et al. 2023

Anal. Chem.

View full text Add to dashboard Cite

Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences in traditional mass spectrometry experiments. Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3and α2,8-linked sialic acids. These chemical modifications were validated and structurally characterized using model isomeric sialic acid conjugates and model protein carriers. Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. In tissues, serum, and cultured cells, this allows for the detection and visualization of Nlinked glycan sialic acid isomers by imaging mass spectrometry approaches. Formalin-fixed paraffinembedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid N-glycans. An azide-amine compound with a poly(ethylene glycol) linker was evaluated for use in histochemical staining. Formalin-fixed pancreatic cancer tissues were amidated with the azide amine, reacted with biotin-alkyne and copper catalyst, and sialic acid isomers detected by streptavidin-peroxidase staining. The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment.

show abstract

Section: Introductionmentioning

confidence: 99%

Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids

McDowell

Blaschke

et al. 2023

Anal. Chem.

View full text Add to dashboard Cite

show abstract

“…The carbohydrate antigen sialyl LewisX is a terminal carbohydrate structure which is associated with tumor malignancy. Sialyl LewisX can serve as a tumor marker and alter cancer cell phenotypes by increasing cancer cell motility and proliferation through E-selectin–mediated cancer cell adhesion to vascular endothelial cells or E-selectin-independent pattern [ 44 , 45 ]. 6-sulfo sialyl LewisX is the sulfation form of sialyl LewisX, in which the GlcNAc is sulfated by specific sulfotransferases.…”

Section: Discussionmentioning

confidence: 99%

CHST2-mediated sulfation of MECA79 antigens is critical for breast cancer cell migration and metastasis

Zhang

Zou

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

Snail is a denoted transcriptional repressor that plays key roles in epithelial-mesenchymal transition (EMT) and metastasis. Lately, a plethora of genes can be induced by stable expression of Snail in multiple cell lines. However, the biological roles of these upregulated genes are largely elusive. Here, we report identification of a gene encoding the key GlcNAc sulfation enzyme CHST2 is induced by Snail in multiple breast cancer cells. Biologically, CHST2 depletion results in inhibition of breast cancer cell migration and metastasis, while overexpression of CHST2 promotes cell migration and lung metastasis in nude mice. In addition, the expression level of MECA79 antigen is elevated and blocking the cell surface MECA79 antigen with specific antibodies can override cell migration mediated by CHST2 upregulation. Moreover, the sulfation inhibitor sodium chlorate effectively inhibits the cell migration induced by CHST2. Collectively, these data provide novel insights into the biology of Snail/CHST2/MECA79 axis in breast cancer progression and metastasis as well as potential therapeutic strategy for the diagnosis and treatment of breast cancer metastasis.

show abstract

“…sLeX is a well known cancer-associated carbohydrate structure [48,64,65]. It plays a vital role in tumor cell metastasis.…”

Section: In Cancersmentioning

confidence: 99%

Essential functions, syntheses and detection of sialyl Lewis X on glycoproteins

Chen

2023

Explor Drug Sci

View full text Add to dashboard Cite

It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell surface. It presents as a terminal structure on either glycoproteins or glycolipids and has been demonstrated to be related to various biological processes, such as fertilization and selectin binding. Due to the vital role of sLeX, its synthesis as well as its determination approaches have attracted considerable attention from many researchers. In this review, the focus is sLeX on glycoproteins. The biological importance of sLeX in fertilization and development, immunity, cancers, and other aspects will be first introduced. Then the chemical and enzymatic synthesis of sLeX including the contributions from more than 15 international research groups will be described, followed by a brief view of the sLeX detection focusing on monosaccharides and linkages. This review is valuable for those readers who are interested in the chemistry and biology of sLeX.

show abstract

The Cancer-Associated Antigens Sialyl Lewisa/x and Sda: Two Opposite Faces of Terminal Glycosylation

Cited by 23 publications

References 95 publications

Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids

Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids

CHST2-mediated sulfation of MECA79 antigens is critical for breast cancer cell migration and metastasis

Essential functions, syntheses and detection of sialyl Lewis X on glycoproteins

Contact Info

Product

Resources

About