Glycoproteomic characterization of carriers of the CD15/Lewisx epitope on Hodgkin's Reed-Sternberg cells

Abstract

BackgroundThe Lewisx trisaccharide, also referred to as the CD15 antigen, is a diagnostic marker used to distinguish Hodgkin's lymphoma from other lymphocytic cancers. However, the role of such fucosylated structures remains poorly understood, in part because carriers of Lewisx structures on Hodgkin's Reed-Sternberg cells have not been identified.MethodsGalMBP, an engineered carbohydrate-recognition protein that binds selectively to oligosaccharides with paired terminal galactose and fucose residues, has been used in conjunction with proteomic and glycomic analysis to identify glycoprotein carriers of Lewisx and related glycan structures in multiple Hodgkin's Reed-Sternberg cell lines.ResultsMultiple glycoproteins that bind to GalMBP and carry CD15/Lewisx have been identified in a panel of six Reed-Sternberg cell lines. The most commonly identified Lewisx-bearing glycoproteins are CD98hc, which was found in all six cell lines tested, and intercellular adhesion molecule-1 and DEC-205, which were detected in five and four of the lines, respectively. Thus, several of the most prominent cell adhesion molecules on the lymphomas carry this characteristic glycan epitope. In addition, the Hodgkin's Reed-Sternberg cell lines can be grouped into subsets based on the presence or absence of less common Lewisx-bearing glycoproteins.ConclusionsCD98 and intercellular adhesion molecule-1 are major carriers of CD15/Lewisx on Reed-Sternberg cells. Binding of DC-SIGN and other glycan-specific receptors to the Lewisx epitopes on CD98 and intercellular adhesion molecule-1 may facilitate interaction of the lymphoma cells with lymphocytes and myeloid cells in lymph nodes.

CD98 at the crossroads of adaptive immunity and cancer

“…Thus, the expression level of CD98hc would fine-tune the capacity of the cell to sense the compliance of the matrix. Indeed, CD98hc is important in (Haynes et al, 1981a) Bladder cancer cells (transitional epithelium) Anti-CD98 antibody treatment inhibits proliferation of human tumor cells (Yagita et al, 1986) B cell lymphomas CD98 expression on lymphomas can identify patients with poor prognosis (Holte et al, 1987;Holte et al, 1989;Salter et al, 1989;Powlesland et al, 2011) Oral squamous cell carcinoma CD98 histological expression pattern within a tumor is a significant indicator of progression and metastasis (Esteban et al, 1990;Kim et al, 2004) Childhood acute lymphoblastic leukemia CD98 expression level correlates with duration of complete remission (Taskov et al, 1996) (Mouse) fibroblast (3T3 cell line) CD98 overexpression leads to transformation (Hara et al, 1999;Henderson et al, 2004;Shishido et al, 2000) Astrocytic neoplasms CD98 light chain (LAT-1) expression is increased in astrocytic cancers (Nawashiro et al, 2002) Human glioblastoma (and rat C6 glioma model)…”

SugarQuant: a streamlined pipeline for multiplexed quantitative site-specific N-glycoproteomics

“…13). For example, the fucosylated glycan epitope, Lewis x , is expressed on Hodgkin's Reed-Sternberg cells (often carried by CD98 and ICAM-1, both are 2FF-affected glycoproteins) and is an established diagnostic marker for patients with Hodgkin's lymphoma 34,35 .…”

Mannose-recognition mutant of the galactose/N-acetylgalactosamine-specific C-type lectin CEL-I engineered by site-directed mutagenesis

“…Therefore, it seems reasonable that glucose, which has the same configuration regarding 3-and 4-hydroxy groups as mannose, can bind to EPNH-CEL-I with a moderate affinity. Along with the findings of the preceding studies on engineering of MBP-A to change its specificity to galactose binding [14,15] and its applications for the identification of cell surface glycoconjugates [38][39][40], a reversal change in the specificity of CEL-I from galactose (N-acetylgalactosamine) to mannose shown in the present study suggests the versatility of C-type CRDs. As observed in glycoconjugate microarray analysis, mutations in CEL-I seem to have affected the recognition of not only monosaccharides but also oligosaccharides.…”