Lectin approaches for glycoproteomics in FDA-approved cancer biomarkers

Abstract

The nine FDA-approved protein biomarkers for the diagnosis and management of cancer are approaching maturity, but their different glycosylation compositions relevant to early diagnosis still remain practically unexplored at the sub-glycoproteome scale. Lectins generally exhibit strong binding to specific sub-glycoproteome components and this property has been quite poorly addressed as the basis for the early diagnosis methods. Here, we discuss some glycoproteome issues that make tackling the glycoproteome particularly challenging in the cancer biomarkers field and include a brief view for next generation technologies.

Concanavalin A immobilized magnetic poly(glycidyl methacrylate) beads for prostate specific antigen binding

“…Therefore, the discovery of a more effective biomarker for the diagnosis of PCa has been raised due to the limitations associated with PSA. It is noteworthy that all cancer biomarkers approved by the US Food and Drug Administration (FDA) have also glycoprotein structure [4]. In this context, the development of materials, capable of adsorbing the glycoproteins including PSA, will enable the discovery of new biomarkers.…”

Harnessing cancer cell metabolism for theranostic applications using metabolic glycoengineering of sialic acid in breast cancer as a pioneering example

“…Specifically, instead of changes being limited to a targeted reduction in highly-branched N-glycans due to the expected selective impact of lower UDP-GlcNAc levels on MGAT4/5 activity, dozens of additional glycan structures were affected with about half increasing in abundance; a reduction in UDP-GlcNAc could not have this effect based on any currently-known mechanism. Second, in recently-published studies we discovered links between metabolism and sialylation that also were not easily explained by direct interplay between metabolic intermediates and biosynthetic enzymes [76, 101]. In particular, cell surface sialylation was rapidly diminished upon induced nutrient deprivation of breast cancer cells evaluated in vitro , which based on the metabolic networks diagramed in Figure 4, initially appears reasonable because UDP-GlcNAc is the metabolic feedstock for sialylation.…”

“…Finally, sialidases emanating from cancer cells can be shed into systemic circulation, where they can cleave sialic acids from serum glycoproteins, which results in the faster clearance of these proteins from circulation. Overall the remodeling of sialylation by the combined action of sialyltransferases and sialidases plays numerous important roles in maintaining health or succumbing to various diseases [101]. …”

Separation of monosaccharides hydrolyzed from glycoproteins without the need for derivatization

“…Characterization of carbohydrates and glycans in biological systems is of critical interest in several diverse areas including therapeutics development [1,2], disease diagnostics (cancer, heart disease, diabetes, and numerous others) [3][4][5], and elucidation of biological processes [6][7][8][9] (cellular metabolism, biosynthesis, and development). Additionally, greater understanding of protein folding [10,11], immunity, energy storage, and other areas are dependent on knowledge of glycan composition.…”