Molecular Basis for Recognition of the Cancer Glycobiomarker, LacdiNAc (GalNAc[β1→4]GlcNAc), by Wisteria floribunda Agglutinin

Haji-Ghassemi, O.; Gilbert, Michel; Spence, Jenifer; Schur, Melissa J.; Parker, Matthew J.; Jenkins, Meredith L.; Burke, John E.; Faassen, Henk van; Young, N. Martin; Evans, Stephen V.

doi:10.1074/jbc.m116.750463

Cited by 50 publications

(45 citation statements)

References 62 publications

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“…PSA from seminal plasma of healthy men and LNCaP-conditioned medium were also simultaneously analysed using the same set of lectin columns. Several reports have shown that the LacdiNAc structure is abundantly expressed in LNCaP cancer cell and this was examined as the cancer-related glycomarker 14,15 ; we measured the amount of PSA with LacdiNAc using Wisteria floribunda agglutinin (WFA) column chromatography. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Study of glycosylation of prostate-specific antigen secreted by cancer tissue-originated spheroids reveals new candidates for prostate cancer detection

Ideo

Kondo

Nomura

et al. 2020

Sci Rep

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Prostate-specific antigen (PSA) is the most frequently used biomarker for the screening of prostate cancer. Understanding the structure of cancer-specific glycans can help us improve PSA assay. In the present study, we analysed the glycans of PSA obtained from culture medium containing cancer tissue-originated spheroids (CTOS) which have similar characteristics as that of the parent tumour to explore the new candidates for cancer-related glycoforms of PSA. The glycan profile of PSA from CTOS was determined by comparing with PSA from normal seminal plasma and cancer cell lines (LNCaP and 22Rv1) using lectin chromatography and mass spectrometry. PSA from CTOS was mostly sialylated and the content of Wisteria floribunda agglutinin reactive glycan (LacdiNAc) was similar to that of PSA derived from seminal plasma and 22Rv1. Conversely, concanavalin A (Con A)-unbound PSA was definitely detected from the three cancer origins but was almost negligible in seminal PSA. Two novel types of PSA were elucidated in the Con A-unbound fraction: one is a high molecular weight PSA with highly branched N-glycans, and the other is a low molecular weight pSA without N-glycans. Furthermore, the existence of Lewis X antigen group on PSA was indicated. These PSAs will be candidates for new cancer-related markers.Prostate-specific antigen (PSA) is a glycoprotein that is exclusively produced by the prostate gland. PSA is normally found in semen, but men with prostate cancer often have a higher amount of PSA in the blood. PSA test is a screening test for prostate cancer; it measures the concentration of PSA in blood. The PSA levels also increase during non-cancerous conditions such as prostatitis (inflammation of the prostate), or benign prostatic hyperplasia (BPH, enlargement of the prostate). Men with PSA levels between 4 and 10 ng/ml have a 25% chance of developing prostate cancer, and this concentration range is known as the diagnostic grey zone. Therefore, a precise diagnosis that can distinguish cancer and inflammatory diseases is required.Numerous studies have reported that aberrant glycosylation occurs in cancer cells rather than in normal cells 1,2 . These cancer-associated modifications of glycans are expected to help in a more precise diagnosis of cancer. Therefore, if aberrant glycans on PSA of cancer origin are present, they are attractive targets and several studies to determine them have been conducted 3 . Peracaula et al. 4 analysed the glycans released from PSA in conditioned medium of LNCaP cancer cell line. The glycans were not sialylated, but they contained a Fucα1-2Gal residue and a high amount of GalNAcβ1-4GlcNAc (LacdiNAc). However, the glycans on PSA from the sera of prostate cancer patients were mostly sialylated and the glycan profiles are not the same as in the LNCaP cell 5,6 . It is well known that cell lines often acquire substantial bias and lose several characteristics of parental tumours during culture establishment and passage 7,8 ; thus, the glycan profiles of such cells may have often changed from primary ...

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Section: Resultsmentioning

confidence: 99%

Study of glycosylation of prostate-specific antigen secreted by cancer tissue-originated spheroids reveals new candidates for prostate cancer detection

Ideo

Kondo

Nomura

et al. 2020

Sci Rep

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“…WFA has been used as a tool for revealing areal borders and subdivisions. As LacdiNAc (β- d -GalNAc-[1→4]- d -GlcNAc) is associated with tumor malignancy in leukemia, prostate, pancreatic, ovarian, and liver cancers, WFA is promising for cancer glycobiomarker detection [ 10 , 39 ]. rD2BPL3 recognizes LacdiNAc, similarly to WFA; thus, rD2BPL3 is strong candidate for the development of a cancer glycobiomarker.…”

Section: Discussionmentioning

confidence: 99%

“…Gal/GalNAc-specific lectin is a vaccine candidate for amoebiasis and a focus of immunogenicity studies [ 9 ]. Wisteria floribunda agglutinin (WFA), a GalNAc-specific lectin, shows promise for cancer biomarker detection, with disaccharide LacdiNAc (β- d -GalNAc-[1→4]- d -GlcNAc) recognition properties [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Functional Expression and Characterization of the Recombinant N-Acetyl-Glucosamine/N-Acetyl-Galactosamine-Specific Marine Algal Lectin BPL3

et al. 2018

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Lectins, characterized by their carbohydrate-binding ability, have extensive practical applications. However, their industrial use is limited due to impurity. Thus, quality-controlled production of recombinant lectin is necessary. In this study, the algal lectin BPL3 (Bryopsis plumosa lectin 3) was successfully produced using a bacterial expression system, BL21(DE3), with an artificial repeated structure (dimeric construct). Recombinant dimeric BPL3 (rD2BPL3) was confirmed by LC-MS/MS spectrometry. Expression efficiency was greater for the construct with the repeat structure (rD2BPL3) than the monomeric form (rD1BPL3). Optimal conditions for expression were 1 mM IPTG at 20 °C. Recombinant lectin was purified under denaturing conditions and refolded by the flash dilution method. Recombinant BPL3 was solubilized in 1× PBS containing 2 M urea. rD2BPL3 showed strong hemagglutination activity using human erythrocyte. rD2BPL3 had a similar sugar specificity to that of the native protein, i.e., to N-acetyl-glucosamine (GlcNAc) and N-acetyl-galactosamine (GalNAc). Glycan array results showed that recombinant BPL3 and native BPL3 exhibited different binding properties. Both showed weak binding activity to α-Man-Sp. Native BPL3 showed strong binding specificity to the alpha conformation of amino sugars, and rD2BPL3 had binding activity to the beta conformation. The process developed in this study was suitable for the quality-controlled large-scale production of recombinant lectins.

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“…Though β-galactosides are generally recognized as Gal-3 ligands, we recently found that the terminal N , N′ -diacetyllactosamine (LacdiNAc; GalNAcβ1,4GlcNAc) epitope acts as a selective ligand of Gal-3 compared to galectin-1 [ 6 , 7 ]. The LacdiNAc disaccharide specifically occurs in some O - and N -linked mammalian glycoproteins and has specialized functions [ 8 , 9 ]; it has also been identified as a specific glyco-biomarker in several types of cancers [ 10 , 11 , 12 ]. Otherwise, it is overexpressed in parasites [ 13 ] and other organisms [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Poly-N-Acetyllactosamine Neo-Glycoproteins as Nanomolar Ligands of Human Galectin-3: Binding Kinetics and Modeling

Bumba

Laaf

Spiwok

et al. 2018

IJMS

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Galectin-3 (Gal-3) is recognized as a prognostic marker in several cancer types. Its involvement in tumor development and proliferation makes this lectin a promising target for early cancer diagnosis and anti-cancer therapies. Gal-3 recognizes poly-N-acetyllactosamine (LacNAc)-based carbohydrate motifs of glycoproteins and glycolipids with a high specificity for internal LacNAc epitopes. This study analyzes the mode and kinetics of binding of Gal-3 to a series of multivalent neo-glycoproteins presenting complex poly-LacNAc-based oligosaccharide ligands on a scaffold of bovine serum albumin. These neo-glycoproteins rank among the strongest Gal-3 ligands reported, with Kd reaching sub-nanomolar values as determined by surface plasmon resonance. Significant differences in the binding kinetics were observed within the ligand series, showing the tetrasaccharide capped with N,N′-diacetyllactosamine (LacdiNAc) as the strongest ligand of Gal-3 in this study. A molecular model of the Gal-3 carbohydrate recognition domain with docked oligosaccharide ligands is presented that shows the relations in the binding site at the molecular level. The neo-glycoproteins presented herein may be applied for selective recognition of Gal-3 both on the cell surface and in blood serum.

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Molecular Basis for Recognition of the Cancer Glycobiomarker, LacdiNAc (GalNAc[β1→4]GlcNAc), by Wisteria floribunda Agglutinin

Cited by 50 publications

References 62 publications

Study of glycosylation of prostate-specific antigen secreted by cancer tissue-originated spheroids reveals new candidates for prostate cancer detection

Study of glycosylation of prostate-specific antigen secreted by cancer tissue-originated spheroids reveals new candidates for prostate cancer detection

Functional Expression and Characterization of the Recombinant N-Acetyl-Glucosamine/N-Acetyl-Galactosamine-Specific Marine Algal Lectin BPL3

Poly-N-Acetyllactosamine Neo-Glycoproteins as Nanomolar Ligands of Human Galectin-3: Binding Kinetics and Modeling

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