Glycans (e.g. N-glycans, O-glycans, and glycosphingolipids) participate in multiple biological processes, such as inflammation, signal transduction, cell-cell interactions, virus/bacteria-host interactions, and cancer development and progression. Commonly, changes in glycosylation are a hallmark of disease states. And cancer cells frequently display glycans at different levels or with basically different structures than those present on normal cells. Creative Biolabs is a professional and years of experienced institute in the field of glycobiology who always keeps a watchful eye on the investigation of altered glycosylation in cancer. With the help of us, clients can attain a better understanding of glycans in oncology.
Fig.1 IgG glycan profiles in eight pairs of twins discordant for renal function. (Pinho, 2015)
Altered glycosylation is a universal characteristic of cancer cells. However, there only certain specific glycan changes are often associated with neoplasms. Such findings involve: increased β1-6GlcNAc branching of N-glycans; increased O-GlcNAcylation on many proteins; truncation of O-glycans, leading to Tn and sialyl Tn antigen expression; alterations in the quantity, linkage, and acetylation of sialic acids; levels of sialylated Lewis structures and selectin ligands; expressions of the nonhuman sialic acid, Neu5Gc; altered expression and enhanced degradation of glycosphingolipids; changes in sulfation of glycosaminoglycans; increased expression of galectins and poly-N-acetyllactosamines; increased expression of hyaluronan; increased expression of enzymes that attach GPI anchors to proteins; and altered expression of ABH(O) blood-group-related structures.
Glycosylation is a process of addition of glycans to proteins or other molecules, and protein glycosylation promotes molecular heterogeneity and functional diversity within cells. It is a major posttranslational modification of proteins which plays a critical role in malignant transformation and metastasis. Glycosylation is produced on the Golgi structure and depends on the action of glycosidases and glycosyltransferases in different cells or tissues. The major glycosylation changes, sialylation, and fucosylation, are typical terminal modifications that mediate vital biological processes and also have implications in cancers.
Fig.2 Role of glycans in cancer development and progression. (Pinho, 2015)
Tumor cells show a wide range of glycosylation alterations compared with their non‑transformed counterparts. Generally, a shift from normal glycosylation pathway occurs in cancer cells, resulting in altered glycans expression due to several factors. First, altered expression of glycans is attributed to low or overexpression of glycosyltransferases. Second, altered glycan levels stem from changes in the tertiary conformation of the peptide backbone and the nascent glycan chain. Third, the differences are on account of the variability of various acceptor substrates along with the availability and abundance of sugar nucleotide donors and cofactors. Ultimately, changes in glycan expression rely on the expression and localization of relevant glycosyltransferases in the Golgi apparatus.
Initially, changes in glycosylation regarding oncogenic transformation were described over more than sixty years ago. Such findings were further confirmed by the advent of monoclonal antibody technology, which displayed tumor-specific antibodies that were directed against carbohydrate epitopes and, in most situations, were oncofetal antigens on tumor glycoproteins and glycosphingolipids. Here, carbohydrate-based anticancer vaccines have been prepared by linking multiple copies of synthetic tumor-associated glycans to the carrier proteins. Meanwhile, several glycan-based vaccines are currently undergoing clinical evaluation and have revealed some promise.
By contrast, drug development strategies of preventing cancer glycans formation or interrupting their downstream interactions can only be effective if these glycans make a significant contribution to the disease. For example, in some cases, the causal link is clear -- certain glycan structure of β1,6GlcNAc-branching and sLex contribute to oncogenic signaling and metastasis.
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