ABSTRACT
The relevance of protein-glycan interactions in immunity has long been underestimated. Yet, the immune system possesses numerous classes of glycan-binding proteins, so-called lectins. Of specific interest is the group of myeloid C-type lectin receptors (CLRs) as they are mainly expressed by myeloid cells and play an important role in the initiation of an immune response. Myeloid CLRs represent a major group amongst pattern recognition receptors (PRRs), placing them at the center of the rapidly growing field of glycoimmunology. CLRs have evolved to encompass a wide range of structures and functions and to recognize a large number of glycans and many other ligands from different classes of biopolymers. This review aims at providing the reader with an overview of myeloid CLRs and selected ligands, while highlighting recent insights into CLR-ligand interactions. Subsequently, methodological approaches in CLR-ligand research will be presented. Finally, this review will discuss how CLR-ligand interactions culminate in immunological functions, how glycan mimicry favors immune escape by pathogens, and in which way immune responses can be affected by CLR-ligand interactions in the long term.
ABSTRACT
Breast cancer is the most frequent cancer diagnosed in women and the second most common cancer-causing death worldwide. The major problem around the management of breast cancer is its high heterogeneity and the development of therapeutic resistance. Therefore, understanding the fundamental breast cancer biology is crucial for better diagnosis and therapy. Protein sialylation is a key posttranslational modification of glycoproteins, which is also involved in tumor progression and metastasis. Increased expression of sialic acids (Sia) can interfere in receptor-ligand interactions and might protect tumor cells from the immune system. Furthermore, Sia content on the cell membrane plays a role in cancer resistance towards chemo- and radiation therapy. In this study, we glycoengineered MCF-7 breast cancer cells using a series of non-natural Sia precursors, which are prolonged in their acyl side chain. We observed a significant reduction in the natural Sia (N-Acetylneuraminic acid) expression after cultivation of MCF-7 cells with these Sia precursors. In addition, the expression of polySia, a unique glycosylation of the neural cell adhesion molecule NCAM, which interferes with cell adhesion, was decreased. We conclude that sialic acid engineering i) opens up novel opportunities to study the biological role of Sia in breast cancer and ii) provides a toolbox to examine the sialic acid-dependent complex cellular alterations in breast cancer cell biology.
Subject(s)
Breast Neoplasms/pathology , Cell Adhesion , Cell Membrane/metabolism , Cell Movement , Glycoproteins/metabolism , Metabolic Engineering , N-Acetylneuraminic Acid/metabolism , Apoptosis , Breast Neoplasms/metabolism , Cell Proliferation , Female , Humans , Neural Cell Adhesion Molecules/metabolism , Tumor Cells, CulturedABSTRACT
Neuroblastoma is the second most frequent extracranial tumor, affecting young children worldwide. One hallmark of tumors such as neuroblastomas, is the expression of polysialic acid, which interferes with adhesion and may promote invasion and metastasis. Since tumor cells use glycolysis for energy production, they thereby produce as side product methylglyoxal (MGO), which reacts with proteins to advanced glycation end products in a mechanism called glycation. Here we analyzed the expression of (poly) sialic acid and adhesion of Kelly neuroblastoma cells after glycation with MGO. We found that both sialylation and polysialylation is increased after glycation. Furthermore, glycated Kelly neuroblastoma cells had a much higher potential for migration and invasion compared with non-glycated cells.
Subject(s)
Glycolysis/genetics , Neuroblastoma/genetics , Sialic Acids/metabolism , Cell Adhesion , Cell Movement , Female , Glycosylation , Humans , Infant , Male , Neoplasm Metastasis , Neuroblastoma/pathologyABSTRACT
Obesity leads to an altered adipocytokine production negatively effecting the function of natural killer cells (NK cells), which are important effector cells of the innate immune system. NK cells provide a defence against tumour cells or virus infected cells and have different activating and inhibitory surface receptors to distinguish between normal and transformed cells. One group of the inhibitory receptors are the sialic acid-binding immunoglobulin-like lectins (Siglecs). The aim of this study was to compare the expression of Siglecs-7, -9 and -10 on NK cells from normal weight and obese subjects. Therefore peripheral blood mononuclear cells (PBMC) were isolated from 10 normal weight (BMI < 25 kg/m2) and 11 obese (BMI > 30 kg/m2) blood donors and analysed by flow cytometry. Moreover, the amount of sialic acid on NK cell was determined using a fluorescent labelled lectin that binds terminal sialic acids. Percentages of immune cells were not altered between normal weight and obese individuals. CD56bright NK cells from obese subjects had a reduced expression of Siglec-7 while the expression of Siglec-9 was not altered. The reduction of Siglec-7 expression on CD56bright NK cells might be a marker for their dysfunction. Moreover, Siglecs-7, -9 and -10 are not expressed on the NK cell lines NK-92 and NKL. When comparing the two NK cell subpopulations CD56bright and CD56dim, CD56bright NK cells had a higher amount of sialic acids on their surface compared to CD56dim NK cells regardless of body weight.
