Plant Lectins in Cancer Treatment: The Case of Viscum album L.
Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri in Plants That Fight Cancer, 2019
Lectins display great potential in cancer therapy and diagnosis by being molecules able to specifically recognize carbohydrates on the cellular membrane and their glycosylation resulting from malignancy (Mody et al. 1995). Cancer is a complex process in which genetic alterations affect and modify cell signaling, functioning, replication rhythm, apoptosis, and metastasis. Cancer cells exhibit irregular glycosylation patterns, and this process plays a significant role in cell development, signaling, interaction, proliferation, differentiation, and migration (Estrada-Martínez et al. 2017). During malignant transformation, the glycans express alterations such as over expression of certain structures, loss of expression, the appearance of novel or incomplete structures, and the accumulation of precursors (Varki et al. 2017). Glycan is a term used for any sugar or assembly of sugars, existing in a free form or attached to molecules. Glycans are involved in basic molecular and biological processes occurring in cancer affecting cell signaling, cell–cell and cell–matrix interactions, tumor cell invasion, angiogenesis, immune modulation, and metastasis (Pinho and Reis 2015). The glycosylation of proteins is the key element for a wide variety of biological processes affecting their localization, stability, and folding. Consequently, aberrant glycosylation in malignant cells results in many biological pathways affecting cell signaling, migration, adhesion, and cell death, regulating apoptosis, and autophagy (Korekane and Taniguchi 2015).
Treatment strategies in assisted reproduction for the poor-responder patient
David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham in Textbook of Assisted Reproductive Techniques, 2017
FSH secreted from the pituitary is a heterodimer glycoprotein hormone with two covalently linked subunits, α and β. The molecule is glycosylated by post-translational modification, and the presence and composition of the carbohydrate glycan moieties determine its in vivo biological activity (Figure 50.6) (190,191). In vivo, the native FSH consists of a family of at least 20 different isohormones that differ in their pattern of glycosylation. For follitropin-α, isoelectric focusing has identified seven major bands of FSH isoforms between pI 4.2 and 5.05, five minor bands between pI 5.25 and 6.30, and one minor band at pI 4.20. These have been demonstrated to be consistent between different manufactured batches (192). The ovarian response to stimulation by FSH relies on an interaction of the hormone with membrane receptors (FSHR) on GCs, and a normal response is dependent on the correct molecular structure of the hormone, the receptor, and factors associated with their interaction. Any defect in the genes encoding FSH or its receptor may result in ovarian resistance, and therefore genotype may play a fundamental role in determining the physiological response to FSH stimulation.
The Acute Phase Response: An Overview
Andrzej Mackiewicz, Irving Kushner, Heinz Baumann in Acute Phase Proteins, 2020
Significant biological roles are played by N-linked glycans of membrane and secretory proteins; different glycoforms of serum APP have been found to have various biological effects. For example, desialylated α1-acid glycoprotein is associated with increased expression of activity inhibitory to platelet aggregation97 or with loss of the ability to inhibit mitogen-induced lymphocyte proliferation.98 The Con A-nonreactive form of serum α1-acid glycoprotein is more effective in the modulation of lymphocyte proliferation99 and induction of release of IL-1 inhibitory activity by monocytes100 than are the Con A-reactive forms. The Con A-nonreactive form of PI is more effective in the inhibition of natural killer cell activity than are Con A-reactive forms.101 More fucosylated antennary structures of α1-acid glycoprotein inhibit the adherence of leukocytes to endothelial cells more effectively.102 Accordingly, changes of the profile of the glycosylation of APP seen during the acute phase response may be associated with altered specific biological activity which affects immune response or clotting.
Human disease glycomics: technology advances enabling protein glycosylation analysis – part 1
Published in Expert Review of Proteomics, 2018
Arun V Everest-Dass, Edward S X Moh, Christopher Ashwood, Abdulrahman M M Shathili, Nicolle H Packer
The currently available technologies of glycan analysis require the release of glycans from their carrier proteins if the detailed structural glycan data in terms of composition, sequence, branching, and linkage are needed to be known. Determination of the heterogeneity of glycosylation at a site-specific level is currently reliant on glycopeptide analysis that provides important glycan composition and occupation data, but only partial glycan structural detail. The new derivatization methods on linkage-specific SAs (α2, 3 and α2, 6) are compatible with glycopeptides [214], and structural modifications on the N-glycan core such as core fucosylation and bisecting GlcNAc can now be identified from glycopeptide tandem MS fragmentation [51,215]; however, structural features such as antennae branching, linkage of outer arm fucosylation, Lewis epitopes, and polylactosamine extensions at particular protein sites in a complex mixture still require improvements in the analytical technologies currently available. The presence or addition of specific structural glycan features on proteins has been shown to be critical to many biological functions, but detailed analysis of the glycan heterogeneity present at a particular site is still required. Clearly, as far as can be seen, MS analysis is the core technology that will solve these shortcomings and we are seeing important steps in intact glycoprotein MS, ion mobility, and software development for spectral interpretation that promise to simplify the analysis of both the correct glycan structure and the specific site heterogeneity.
Glycans: potential therapeutic targets for cholangiocarcinoma and their therapeutic and diagnostic implications
Published in Expert Opinion on Therapeutic Targets, 2021
Atit Silsirivanit
Glycosylation is an important post-translational modification of cellular glycoprotein by the stepwise addition of sugar residues to form a complex glycan structure. Glycans play essential roles in many biological processes; such as cell-cell communication, cell adhesion, ligand–receptor interaction, self and nonself recognition, etc. Alteration of glycosylation has been considered a hallmark of cancer as it plays important role in tumor development and progression [1]. The aberrant glycosylation is possibly triggered by the overproduction of nucleotide-sugar donors and/or altered expression of glycosyltransferase and glycosidase enzymes [2]. Not only aberrant glycosylation, but the over-expression of carrier-proteins is also an important factor to promote tumor growth and metastasis. These aberrations are possibly the targets for cancer immunotherapy or chemo-sensitization. Also, the cancer-associated glycans and glycoconjugates can possibly be the biomarkers for diagnosis, monitoring, and prognostic prediction of the disease. Collective data in cholangiocarcinoma (CCA) revealed that glycosylation is altered during tumorigenesis and progression of CCA. The CCA-associated glycans were aberrantly expressed and play many essential roles in tumor metastasis and drug resistance, which were possibly used as the targets for CCA treatment. Moreover, the CCA-associated glycans that are elevated in patients’ sera are beneficial as biomarkers for diagnosis and prognosis of CCA.
Novel methods in glycomics: a 2019 update
Published in Expert Review of Proteomics, 2020
Wei-Qian Cao, Ming-Qi Liu, Si-Yuan Kong, Meng-Xi Wu, Zheng-Ze Huang, Peng-Yuan Yang
Efficient glycomic methods have greatly advanced glycomics in the past dozen years. With advances in glycomic methods, glycomics not only generates a partial list of glycans in a given cell type or tissue but also provides more comprehensive information, such as glycan attachment sites and the spatial organization of glycans in tissues, and thereby facilitates glycobiological research [257]. Glycomics are moving toward both generic and precise analysis. This process, however, raises several key issues that need to be addressed. For example, the lack of release methods and the very low abundance of O-glycans have been major barriers preventing the identification of the native O-glycome. Glycan isoform analysis and site-specific glycan analysis have always been the two most challenging tasks in glycomics due to the inherent complexity of glycans. Accurate solutions for the identification of labile modifications identification on glycans are needed. Low ionization of glycans is still the main problem in MS analysis. The spatial and temporal analysis of glycans is the new tough nut to crack since glycans are highly dynamic and unevenly distributed. Understanding the scope and scale of the functional roles of glycans in organisms and their impact on human disease will first requires detailed characterization of the glycomes of tissues or even cells. Extensive development is still needed to achieve the exquisite and superb technology necessary for complete characterization.