scholarly journals Siglecs as Therapeutic Targets in Cancer

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1178
Author(s):  
Jackwee Lim ◽  
Duygu Sari-Ak ◽  
Tanaya Bagga
Keyword(s):  
Sialic Acid ◽  
Immune Responses ◽  
Cancer Cell ◽  
Immune Cells ◽  
Sialic Acids ◽  
Immune Responsiveness ◽  
Post Translational Modification ◽  
Cell Surfaces ◽  
Molecular Pattern ◽  
Keto Acids

Hypersialylation is a common post-translational modification of protein and lipids found on cancer cell surfaces, which participate in cell-cell interactions and in the regulation of immune responses. Sialic acids are a family of nine-carbon α-keto acids found at the outermost ends of glycans attached to cell surfaces. Given their locations on cell surfaces, tumor cells aberrantly overexpress sialic acids, which are recognized by Siglec receptors found on immune cells to mediate broad immunomodulatory signaling. Enhanced sialylation exposed on cancer cell surfaces is exemplified as “self-associated molecular pattern” (SAMP), which tricks Siglec receptors found on leukocytes to greatly down-regulate immune responsiveness, leading to tumor growth. In this review, we focused on all 15 human Siglecs (including Siglec XII), many of which still remain understudied. We also highlighted strategies that disrupt the course of Siglec-sialic acid interactions, such as antibody-based therapies and sialic acid mimetics leading to tumor cell depletion. Herein, we introduced the central roles of Siglecs in mediating pro-tumor immunity and discussed strategies that target these receptors, which could benefit improved cancer immunotherapy.

A thin hydrogel barrier linked onto cell surface sialic acids through covalent bonds induces cancer cell death in vivo

2020 ◽  
Vol 8 (2) ◽  
pp. 577-585 ◽  
Author(s):  
Kimika Ono ◽  
Yuka Sanada ◽  
Yuka Kimura ◽  
Seika Aoyama ◽  
Natsumi Ueda ◽  
...  
Keyword(s):  
Cell Death ◽  
Sialic Acid ◽  
Cell Surface ◽  
Cancer Cell ◽  
Sialic Acids ◽  
Cell Surfaces ◽  
Covalent Bonds ◽  
Novel Technique ◽  
Cancer Cell Death

A novel technique to form a thin hydrogel barrier on aberrantly expressed sialic acid residues on cancer cell surfaces was developed.

scholarly journals Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces

2021 ◽  
Author(s):  
Yixuan Xie ◽  
Siyu Chen ◽  
Qiongyu Li ◽  
Ying Sheng ◽  
Michael R Alvarez ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Sialic Acid ◽  
Membrane Proteins ◽  
Cell Membranes ◽  
Sialic Acids ◽  
Cross Linking ◽  
Protein Networks ◽  
Cell Surfaces ◽  
Protein Cross Linking

A cross-linking method is developed to elucidate the glycan-mediated interactions between membrane proteins through sialic acids. The method provides previously unknown extensive glycomic interactions on cell membranes. The vast majority...

scholarly journals The investigation of the changes in the surface glycoconjugates using two different spheroid models of breast cancer cells and availability assessment of these spheroid models for rapid diagnosis

2021 ◽  
Vol 38 (3) ◽  
pp. 266-271
Author(s):  
Yosun MATER ◽  
Günnur DEMİRCAN
Keyword(s):  
Breast Cancer ◽  
Cell Culture ◽  
Sialic Acid ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Wheat Germ Agglutinin ◽  
Wheat Germ ◽  
Sialic Acids ◽  
Maackia Amurensis ◽  
Maackia Amurensis Lectin

The importance of early cancer diagnosis has led to development of many different diagnostic methods. In this context, the studies investigating the presence and amount of sugar residues to use as indicators in the identification of cancer cell type have become prominent. In the present study, sialic acids found on the membrane surfaces of ER (+) MCF-7 and ER (-) MDA-MB-231 breast cancer cell lines were labeled using three-dimensional (3D) cell culture (Spheroid) model as the closest method to the patient sample, thus its natural environment, among the cell culture methods. These sugar units that play a role in regulation of important immune characteristics such as recognition, binding and metastasis were made visualizable by applying fluorescent-labeled lectins such as FITC-(Wheat Germ Agglutinin) specifically binding to sialic acid units (GlcNAc, Neu5Ac) including particularly ß-GlcNAc and FITC-(Maackia Amurensis-Lectin-1) specifically binding to Galß4GlcNAc type sialic acids. These glycan units were specifically labeled with FITC-(Maackia Amurensis-Lectin-1) and FITC- (Wheat Germ Agglutinin) and radiation intensities were analyzed relatively. The two different breast cancer cell cultures were compared with respect to change in the amounts of sialic acid residues containing α-2,3- and α-2,6 bonds using fluorescent-labeled lectins. In the present study, we have performed a precise, accurate and rapid determination of the sugar content in the different breast cancer cell surface lines by means of fluorescent-labeled lectins and carried out a relative comparison between the micrographs.

Boronic acid recognition based-gold nanoparticle-labeling strategy for the assay of sialic acid expression on cancer cell surface by inductively coupled plasma mass spectrometry

The Analyst ◽  
2016 ◽  
Vol 141 (4) ◽  
pp. 1286-1293 ◽  
Author(s):  
Xing Zhang ◽  
Beibei Chen ◽  
Man He ◽  
Yuan Zhang ◽  
Lu Peng ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Sialic Acid ◽  
Cell Surface ◽  
Cancer Cell ◽  
Boronic Acid ◽  
Inductively Coupled Plasma ◽  
Normal Cell ◽  
Sialic Acids ◽  
Inductively Coupled ◽  
Plasma Mass Spectrometry

Sialic acids are special sugars widely expressed at the termini of glycan chains on the cell surface, and their expression level on the cancer cell surface is much higher than on the normal cell surface.

scholarly journals Post-conversion sialylation of prions in lymphoid tissues

2015 ◽  
Vol 112 (48) ◽  
pp. E6654-E6662 ◽  
Author(s):  
Saurabh Srivastava ◽  
Natallia Makarava ◽  
Elizaveta Katorcha ◽  
Regina Savtchenko ◽  
Reinhard Brossmer ◽  
...  
Keyword(s):  
Immune System ◽  
Sialic Acid ◽  
Mammalian Cells ◽  
Sialic Acids ◽  
Raw 264.7 Cells ◽  
Lymphoid Tissues ◽  
Host Immune System ◽  
Molecular Pattern ◽  
Secondary Lymphoid Organs

Sialylated glycans on the surface of mammalian cells act as part of a “self-associated molecular pattern,” helping the immune system to recognize “self” from “altered self” or “nonself.” To escape the host immune system, some bacterial pathogens have evolved biosynthetic pathways for host-like sialic acids, whereas others recruited host sialic acids for decorating their surfaces. Prions lack nucleic acids and are not conventional pathogens. Nevertheless, prions might use a similar strategy for invading and colonizing the lymphoreticular system. Here we show that the sialylation status of the infectious, disease-associated state of the prion protein (PrPSc) changes with colonization of secondary lymphoid organs (SLOs). As a result, spleen-derived PrPSc is more sialylated than brain-derived PrPSc. Enhanced sialylation of PrPSc is recapitulated in vitro by incubating brain-derived PrPSc with primary splenocytes or cultured macrophage RAW 264.7 cells. General inhibitors of sialyltranserases (STs), the enzymes that transfer sialic acid residues onto terminal positions of glycans, suppressed extrasialylation of PrPSc. A fluorescently labeled precursor of sialic acid revealed ST activity associated with RAW macrophages. This study illustrates that, upon colonization of SLOs, the sialylation status of prions changes by host STs. We propose that this mechanism is responsible for camouflaging prions in SLOs and has broad implications.

scholarly journals Could Antigen Presenting Cells Represent a Protective Element during SARS-CoV-2 Infection in Children?

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 476
Author(s):  
Rita Lauro ◽  
Natasha Irrera ◽  
Ali H. Eid ◽  
Alessandra Bitto
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Antigen Presenting Cells ◽  
Immune Responsiveness ◽  
Protective Element ◽  
Adults And Children ◽  
Antigen Presenting ◽  
Two Populations

Antigen Presenting Cells (APC) are immune cells that recognize, process, and present antigens to lymphocytes. APCs are among the earliest immune responders against an antigen. Thus, in patients with COVID-19, a disease caused by the newly reported SARS-CoV-2 virus, the role of APCs becomes increasingly important. In this paper, we dissect the role of these cells in the fight against SARS-CoV-2. Interestingly, this virus appears to cause a higher mortality among adults than children. This may suggest that the immune system, particularly APCs, of children may be different from that of adults, which may then explain differences in immune responses between these two populations, evident as different pathological outcome. However, the underlying molecular mechanisms that differentiate juvenile from other APCs are not well understood. Whether juvenile APCs are one reason why children are less susceptible to SARS-CoV-2 requires much attention. The goal of this review is to examine the role of APCs, both in adults and children. The molecular mechanisms governing APCs, especially against SARS-CoV-2, may explain the differential immune responsiveness in the two populations.

scholarly journals Cellular and Molecular Engineering of Glycan Sialylation in Heterologous Systems

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5950
Author(s):  
Ryoma Hombu ◽  
Sriram Neelamegham ◽  
Sheldon Park
Keyword(s):  
Signal Transduction ◽  
Sialic Acid ◽  
Molecular Interactions ◽  
Future Development ◽  
Biological Significance ◽  
Sialic Acids ◽  
Molecular Engineering ◽  
Biological Processes ◽  
Cell Surfaces ◽  
Targeted Disruption

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.

COMPARATIVE ACTION OF VARIOUS OESTROGENIC COMPOUNDS ON MOUSE VAGINAL SIALIC ACIDS (II)

1969 ◽  
Vol 62 (4) ◽  
pp. 663-670 ◽  
Author(s):  
Lars Carlborg
Keyword(s):  
Sialic Acid ◽  
Response Curve ◽  
Sialic Acids ◽  
Clear Cut ◽  
Suitable Parameter ◽  
Sufficient Degree ◽  
Comparative Action ◽  
Relative Potencies ◽  
Good Agreement

ABSTRACT Oestrogens administered in lower doses than necessary to induce full cornification of the mouse vagina induce mucification. It was shown previously that the degree of mucification could be estimated by quantitative determination of sialic acids. A suitable parameter for oestrogen assay was the measurement of vaginal sialic acid concentration which exhibited a clear cut dose response curve. Eleven assays of various oestrogens were performed with this method. Their estimated relative potencies were in good agreement with other routine oestrogen assays. A statistically sufficient degree of precision was found. The sensitivity was of the same order, or slightly higher, than the Allen-Doisy test.

Interspecific variation of zona pellucida glycoconjugates in several species of marsupial

Reproduction ◽  
2000 ◽  
pp. 111-120 ◽  
Author(s):  
JA Chapman ◽  
OW Wiebkin ◽  
WG Breed
Keyword(s):  
Glycine Max ◽  
Sialic Acid ◽  
Zona Pellucida ◽  
Fluorescein Isothiocyanate ◽  
Interspecific Variation ◽  
Lectin Histochemistry ◽  
Sialic Acids ◽  
Arachis Hypogea ◽  
Marsupial Species ◽  
Similar Intensity

The zona pellucida glycoconjugate content of several marsupial species was investigated using differential lectin histochemistry. Ovaries from fat-tailed dunnarts, a southern brown bandicoot, grey short-tailed opossums, brushtail possums, ringtail possums, koalas and eastern grey kangaroos were fixed, embedded in paraffin wax, sectioned and stained with ten fluorescein isothiocyanate-conjugated lectins. Sections were also incubated with either neuraminidase or saponified, respectively, before incubation with the lectins to identify saccharide residues masked by sialic acids or O-acetyl groups on sialic acids. The zonae pellucidae surrounding the oocytes of the marsupials demonstrated interspecific variation in glycoconjugate content, with mannose-containing glycoconjugates exhibiting the greatest variation. Some of the zona pellucida glycoconjugates of all species, except those of the opossums, were masked by sialic acid with an increase in fluorescence with lectins from Arachis hypogea (PNA), and Glycine max (SBA), after desialylation. The disaccharide beta-galactose(1-4)N-acetyl-D-glucosamine appeared to be conformationally masked by O-acetyl groups of sialic acids in the zonae pellucidae of all species, with an increase in fluorescence with the lectin from Erythrina cristagalli (ECA), after saponification. Similar intensity and localization of beta-(1-4)-N-acetyl-D-glucosamine, as shown by staining of the lectin from Triticum vulgaris (WGA), to the inner and outer regions of the zona pellucida, were found to those reported in eutherian species. WGA fluorescence became uniform throughout the zonae pellucidae after saponification, indicating differential O-acetylation of sialic acids on the internal compartment of the zonae pellucidae.

scholarly journals Sialic Acids and Their Influence on Human NK Cell Function

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 263
Author(s):  
Philip Rosenstock ◽  
Thomas Kaufmann
Keyword(s):  
Nk Cells ◽  
Immune Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Sialic Acids ◽  
Innate Immune ◽  
Target Cells ◽  
Carbon Backbone ◽  
Nk Cell Receptors ◽  
Cell Inhibition

Sialic acids are sugars with a nine-carbon backbone, present on the surface of all cells in humans, including immune cells and their target cells, with various functions. Natural Killer (NK) cells are cells of the innate immune system, capable of killing virus-infected and tumor cells. Sialic acids can influence the interaction of NK cells with potential targets in several ways. Different NK cell receptors can bind sialic acids, leading to NK cell inhibition or activation. Moreover, NK cells have sialic acids on their surface, which can regulate receptor abundance and activity. This review is focused on how sialic acids on NK cells and their target cells are involved in NK cell function.

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