Glycosylation in lymphoma: Biology and glycotherapy

Abstract

Research using mouse lymphoma cell lines has resulted in many reports of glycosylation being a key regulator for the distant metastasis of mouse lymphoma cells in animal models. In contrast, there are only a few reports of experiments examining human lymphoma cell metastasis. The glycosylation pattern in human lymphoma shows that loss of Phaseolus vulgaris leukoagglutinating lectin (L‐PHA) reactive oligosaccharides, and sialylation of L‐PHA reactive oligosaccharides, are closely associated with a worse prognosis for diffuse large B cell lymphoma (DLBCL) patients. Sialic acid is related to cell adhesion to the extracellular matrix and metastasis of HBL‐8 Burkitt lymphoma cells in a severe combined immunodeficiency (SCID) mouse animal model. In HBL‐8 clones, differential cell surface sialylation was due to different expression levels of UDP‐GlcNAc 2‐epimerase (GNE). Knockdown of beta‐galactoside alpha‐2,6‐sialyltransferase (ST6Gal1) resulted in enhanced lymphoma cell adhesion to galectin‐1 in anaplastic large cell lymphoma cell line, H‐ALCL. A fluorinated sialic acid analogue was shown to be useful for inhibiting sialyltransferase and may provide a new glycoengineering strategy for desialylation, as well as inhibiting invasion and metastasis and inducing cell death in lymphoma cell lines. This paper discusses glycosylation and sialylation in human lymphoma, and several glycoengineering therapeutic strategies for lymphoma.

Proteogenomic characterization of pancreatic ductal adenocarcinoma

“…N-linked glycosylation occurs in the endoplasmic reticulum and Golgi apparatus and is mediated by the activity of a series of glycosidases and glycosyltransferases (Bieberich, 2014;Cao et al, 2018). Abnormal expressions of sialylated glycoproteins have been uncovered in various solid malignancies, including PDAC, and have been associated with invasiveness and metastatic potential (Hsieh et al, 2017;Suzuki, 2019 , 2016). Here, we have shown that most upregulated N-linked glycoproteins in PDAC are modified by sialylated glycans, consistent with upregulation of ST6GAL1 and ST3GAL1 in PDACs relative to NATs (Figure 4).…”

A case of Burkitt's lymphoma detected with tumor cells clustering in urine

“…Regarding the clustering of non‐epithelial tumor cells, however, only the findings are mentioned in these reports; the mechanism is not mentioned. Recently, in an interesting study, it was stated that sialylic acid, which is one of the cell adhesion molecules, is expressed in BL cell lines 7 . This molecule contributes to the tendency of lymphoma cell metastasis.…”

Glycoprotein PTGDS promotes tumorigenesis of diffuse large B-cell lymphoma by MYH9-mediated regulation of Wnt–β-catenin–STAT3 signaling

“…Post-transcriptional and post-translational modifications have effects on biological activity, subcellular location, and protein stability [ 44 , 45 ]. Besides, abnormal glycosylation has been involved in several diseases [ 46 ] and recent studies found that glycosylation had important roles in lymphoma cell biology [ 47 ], therapy [ 48 , 49 ], and prognosis [ 50 ]. Our results indicated the N-glycosylation sites of PTGDS (Asn51 and Asn78) in DLBCL, which was in agreement with the previous study [ 51 ].…”