Increased expression of the high‑mannose M6N2 and NeuAc3H3N3M3N2F tri‑antennary N‑glycans in cholangiocarcinoma

Talabnin, Krajang; Talabnin, Chutima; Ishihara, Mayumi; Azadi, Parastoo

doi:10.3892/ol.2017.7384

Cited by 19 publications

(15 citation statements)

References 28 publications

(33 reference statements)

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“…In our study, high-mannose (M9) and core-fucosylated (FA2G2S1) plasma glycan species were significantly decreased in the PTSD group, compared to the low-stress healthy control, and this result corresponds to lower glycan species found in inflammation [34]. As alternations of high-mannose glycans have been associated with occurrence and progression of different types of cancers [38][39][40], neuropsychiatric disorders [41], inflammation [34] and brain aging [42], whereas PTSD is associated with inflammation [17] and cardiometabolic disorders [4,5], the lower FA2G2S1 glycan result suggests that veterans with PTSD should be closely monitored for these disorders.…”

Section: N-glycans In Plasmasupporting

confidence: 47%

N-glycomic Profile in Combat Related Post-Traumatic Stress Disorder

et al. 2019

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Post-traumatic stress disorder (PTSD) develops in a portion of individuals exposed to extreme trauma. Glycosylation is a post-translational modification that affects protein functions and is altered in various pathophysiological states and aging. There are still no validated biomarkers of PTSD. The aim of this study was to evaluate the N-glycomic profile in 543 male Caucasian individuals (299 veterans with PTSD and 244 control subjects). The study included discovery (N = 233) and replication (N = 310) cohort. Hydrophilic interaction HPLC and ultra-performance liquid chromatography were used to separate and detect 39 plasma and 24 IgG N-glycan species, respectively. All results were corrected for the effects of age and multiple testing. Significant results included only significantly altered N-glycans in cases/controls in both cohorts, in the same direction. Results showed that six plasma N-glycans (four increased and two decreased) were altered in PTSD vs. controls in both cohorts, but IgG N-glycans were similar between groups. The severity of PTSD was not associated with different plasma N-glycans. This is the first study detecting alterations in plasma N-glycans in PTSD. These N-glycans are also associated with other neuropsychiatric disorders and inflammation, suggesting possible shared glycosylation mechanisms.

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Section: N-glycans In Plasmasupporting

confidence: 47%

N-glycomic Profile in Combat Related Post-Traumatic Stress Disorder

et al. 2019

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“…Earlier studies affirm that while glycans regulate the catalytic activity of certain proteins, others may not be affected by glycosylation changes (29,43). The ability to trace glycans to their parent proteins is necessary to interpret how alterations in glycan expression patterns lead to enhancement of metastatic phenotypes but is lacking in earlier studies (44). Our approach evaluated extended high-mannose glycans together with their parent glycoproteins.…”

Section: Discussionmentioning

confidence: 99%

Metastasis of cholangiocarcinoma is promoted by extended high-mannose glycans

Park

Phoomak

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Membrane-bound oligosaccharides form the interfacial boundary between the cell and its environment, mediating processes such as adhesion and signaling. These structures can undergo dynamic changes in composition and expression based on cell type, external stimuli, and genetic factors. Glycosylation, therefore, is a promising target of therapeutic interventions for presently incurable forms of advanced cancer. Here, we show that cholangiocarcinoma metastasis is characterized by down-regulation of the Golgi α-mannosidase I coding geneMAN1A1, leading to elevation of extended high-mannose glycans with terminating α-1,2-mannose residues. Subsequent reshaping of the glycome by inhibiting α-mannosidase I resulted in significantly higher migratory and invasive capabilities while masking cell surface mannosylation suppressed metastasis-related phenotypes. Exclusive elucidation of differentially expressed membrane glycoproteins and molecular modeling suggested that extended high-mannose glycosylation at the helical domain of transferrin receptor protein 1 promotes conformational changes that improve noncovalent interaction energies and lead to enhancement of cell migration in metastatic cholangiocarcinoma. The results provide support that α-1,2-mannosylatedN-glycans present on cancer cell membrane proteins may serve as therapeutic targets for preventing metastasis.

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“… 12 Notably, a lectin microarray-based sero-biomarker has been reported for the detection of O -linked glycosylation in patients with cholangiocarcinoma; 13 cholangiocarcinoma cell lines exhibit differential expression of O -glycans, based on the histological type of cholangiocarcinoma. 14 Our prior research revealed elevated expression of N -linked glycoprotein glycans in serum from patients with cholangiocarcinoma, compared with healthy controls; 15 elevated glycosphingolipid levels have also been associated with shorter survival in patients with cholangiocarcinoma. 16 …”

Section: Introductionmentioning

confidence: 98%

Ganglioside GM2: a potential biomarker for cholangiocarcinoma

Talabnin

Kumagai

et al. 2020

J Int Med Res

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Objective To investigate the expression of glycosphingolipids in serum and tissue from patients with cholangiocarcinoma compared with healthy controls. Methods Nanospray ionization-linear ion trap mass spectrometry (NSI-MSn) was used to demonstrate the comparative structural glycomics of glycosphingolipids in serum from patients with cholangiocarcinoma (n=15), compared with healthy controls (n = 15). GM2 expression in cholangiocarcinoma tissues (n = 60) was evaluated by immunohistochemistry. Results Eleven glycosphingolipids were detected by NSI-MSn: CMH (ceramide monohexose), Lac-Cer (galactose (Gal)β1-4 glucose (Glc)β1-1'-ceramide), Gb3 (Galα1-4Galβ1-4Glcβ1-1'-ceramide), Gb4/Lc4 (N-acetylgalactosamine (GalNAc)β1-3Galα1-4Galβ1-4Glcβ1-1'-ceramide/Galβ1-4 N-acetylglucosamine (GlcNAc)β1-3Galβ1-4Glcβ1-1'-ceramide), GM3 (N-acetylneuraminic acid (NeuAc)2-3Galβ1-4Glcβ1-1'-ceramide), GM2 (GalNAcβ1-4[NeuAc2-3]Galβ1-4Glcβ1-1'-ceramide), GM1 (Galβ1-3GalNAcβ1-4[NeuAc2-3]Galβ1-4Glcβ1-1'-ceramide), hFA (hydroxylated fatty acid)-CMH, hFA-Lac-Cer, hFA-Gb3, and hFA-GM3. Lac-Cer was the most abundant structure among the lactosides and globosides (normal, 24.40% ± 0.11%; tumor, 24.61% ± 2.10%), while GM3 predominated among the gangliosides (normal, 29.14% ± 1.31%; tumor, 30.53% ± 4.04%). The two glycosphingolipids that significantly differed between healthy controls and patients with cholangiocarcinoma were Gb3 and GM2. High expression of GM2 was associated with vascular invasion in tissue from patients with cholangiocarcinoma. Conclusions Altered expression of glycosphingolipids in tissue and serum from patients with cholangiocarcinoma may contribute to tumor growth and progression. The ganglioside GM2, which significantly increased in the serum of patients with cholangiocarcinoma, represents a promising target as a biomarker for cholangiocarcinoma.

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Increased expression of the high‑mannose M6N2 and NeuAc3H3N3M3N2F tri‑antennary N‑glycans in cholangiocarcinoma

Cited by 19 publications

References 28 publications

N-glycomic Profile in Combat Related Post-Traumatic Stress Disorder

N-glycomic Profile in Combat Related Post-Traumatic Stress Disorder

Metastasis of cholangiocarcinoma is promoted by extended high-mannose glycans

Ganglioside GM2: a potential biomarker for cholangiocarcinoma

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