Aberrant Glycosylation as Biomarker for Cancer: Focus on CD43

Abstract

Glycosylation is a posttranslational modification of proteins playing a major role in cell signalling, immune recognition, and cell-cell interaction because of their glycan branches conferring structure variability and binding specificity to lectin ligands. Aberrant expression of glycan structures as well as occurrence of truncated structures, precursors, or novel structures of glycan may affect ligand-receptor interactions and thus interfere with regulation of cell adhesion, migration, and proliferation. Indeed, aberrant glycosylation represents a hallmark of cancer, reflecting cancer-specific changes in glycan biosynthesis pathways such as the altered expression of glycosyltransferases and glycosidases. Most studies have been carried out to identify changes in serum glycan structures. In most cancers, fucosylation and sialylation are significantly modified. Thus, aberrations in glycan structures can be used as targets to improve existing serum cancer biomarkers. The ability to distinguish differences in the glycosylation of proteins between cancer and control patients emphasizes glycobiology as a promising field for potential biomarker identification. In this review, we discuss the aberrant protein glycosylation associated with human cancer and the identification of protein glycoforms as cancer biomarkers. In particular, we will focus on the aberrant CD43 glycosylation as cancer biomarker and the potential to exploit the UN1 monoclonal antibody (UN1 mAb) to identify aberrant CD43 glycoforms.

Susceptibility to proteases of anti-Tn-antigen MLS128 binding glycoproteins expressed in human colon cancer cells

“…Glycophorin A consisting of 131 amino acid residues contains 15 O-glycans and one N-glycan at Asn 45 whereas leukosialin consists of 381 amino acids in which 29 Ser/Thr are O-glycosylated and Asn 239 is N-glycosylated. Apparent molecular masses of glycophoryn A and leukosialin were reported to be 36 and 50-150 kDa (9)(10)(11)(12). Size wise, leukosialin is close to a 110 kDa GP.…”

“…The different molecular masses were shown to be caused by expression of distinct patterns of O-linked oligosaccharides that are specific to each cell type (12). Leukosialin, also known as CD43, was originally found in hematopoietic cells (12), but later identified in a variety of nonhematopoietic cancers including lung, breast, and colon (11). Aberrant glycosylation of leukosialin/CD43 in various cancers must have resulted in apparent molecular masses of 50-150 kDa (11).…”

“…Leukosialin, also known as CD43, was originally found in hematopoietic cells (12), but later identified in a variety of nonhematopoietic cancers including lung, breast, and colon (11). Aberrant glycosylation of leukosialin/CD43 in various cancers must have resulted in apparent molecular masses of 50-150 kDa (11). Monoclonal antibody called UN1 recognizes a heavily sialylated and O-glycosylated protein with apparent molecular weight of 100-120 kDa.…”

UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase- 6 (pp-GalNAc-T6): Role in Cancer and Prospects as a Drug Target

“…Elevated levels indicate a poor prognosis or treatment failure. CA15-3 cannot be used for screening purposes as it is not only expressed in breast cancer but also in other cancers, as well as some inflammatory conditions such as ovarian hyperstimulation syndrome [59]. pp-GalNAc-T6 itself has potential as a biomarker since it is up-regulated in many types of cancer.…”

Recognition of N-Glycoforms in Human Chorionic Gonadotropin by Monoclonal Antibodies and Their Interaction Motifs

“…The majority of these biomarkers are glycoproteins (4). The abnormal glycosylation of proteins has been revealed to participate in the occurrence and development of many diseases, including various cancers (5,6). For example, aberrant prostate specific antigen glycosylation is associated with prostate cancer (7).…”