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Combined sialic acid and HDAC inhibitor treatment upregulates the neuroblastoma antigen GD2

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Combined sialic acid and HDAC inhibitor treatment upregulates the neuroblastoma antigen GD2. / van den Bijgaart, Renske J E; Kroesen, Michiel; Wassink, Melissa; Brok, Ingrid C; Kers-Rebel, Esther D; Boon, Louis; Heise, Torben; van Scherpenzeel, Monique; Lefeber, Dirk J; Boltje, Thomas J; den Brok, Martijn H; Hoogerbrugge, Peter M; Büll, Christian; Adema, Gosse J.

I: The Journal of Biological Chemistry, 2019, s. 4437-4449.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

van den Bijgaart, RJE, Kroesen, M, Wassink, M, Brok, IC, Kers-Rebel, ED, Boon, L, Heise, T, van Scherpenzeel, M, Lefeber, DJ, Boltje, TJ, den Brok, MH, Hoogerbrugge, PM, Büll, C & Adema, GJ 2019, 'Combined sialic acid and HDAC inhibitor treatment upregulates the neuroblastoma antigen GD2', The Journal of Biological Chemistry, s. 4437-4449. https://doi.org/10.1074/jbc.RA118.002763

APA

van den Bijgaart, R. J. E., Kroesen, M., Wassink, M., Brok, I. C., Kers-Rebel, E. D., Boon, L., ... Adema, G. J. (2019). Combined sialic acid and HDAC inhibitor treatment upregulates the neuroblastoma antigen GD2. The Journal of Biological Chemistry, 4437-4449. https://doi.org/10.1074/jbc.RA118.002763

Vancouver

van den Bijgaart RJE, Kroesen M, Wassink M, Brok IC, Kers-Rebel ED, Boon L o.a. Combined sialic acid and HDAC inhibitor treatment upregulates the neuroblastoma antigen GD2. The Journal of Biological Chemistry. 2019;4437-4449. https://doi.org/10.1074/jbc.RA118.002763

Author

van den Bijgaart, Renske J E ; Kroesen, Michiel ; Wassink, Melissa ; Brok, Ingrid C ; Kers-Rebel, Esther D ; Boon, Louis ; Heise, Torben ; van Scherpenzeel, Monique ; Lefeber, Dirk J ; Boltje, Thomas J ; den Brok, Martijn H ; Hoogerbrugge, Peter M ; Büll, Christian ; Adema, Gosse J. / Combined sialic acid and HDAC inhibitor treatment upregulates the neuroblastoma antigen GD2. I: The Journal of Biological Chemistry. 2019 ; s. 4437-4449.

Bibtex

@article{c8cc73e3942e44b4b2bff47836a58d84,
title = "Combined sialic acid and HDAC inhibitor treatment upregulates the neuroblastoma antigen GD2",
abstract = "Neuroblastoma cells highly express the disialoganglioside GD2, a tumor-associated carbohydrate antigen, which is only sparsely expressed on healthy tissue. GD2 is a primary target for the development of immunotherapy for neuroblastoma. Immunotherapy with monoclonal anti-GD2 antibodies has proven safety and efficacy in clinical trials and is included in the standard treatment for children with high-risk neuroblastoma. Strategies to modulate GD2 expression in neuroblastoma could further improve anti-GD2 targeted immunotherapy. Here, we report that the cellular sialylation pathway as well as epigenetic reprogramming strongly modulate GD2 expression in human and mouse neuroblastoma cell lines. Recognition of GD2 by the 14G2a antibody is sialic acid-dependent and was blocked with the fluorinated sialic acid mimetic Ac53FaxNeu5Ac. Interestingly, sialic acid supplementation using a cell-permeable sialic acid analogue (Ac5Neu5Ac) boosted GD2 expression without or with minor alterations in overall cell surface sialylation. Furthermore, sialic acid supplementation with Ac5Neu5Ac combined with various histone deacetylase (HDAC) inhibitors, including Vorinostat, enhanced GD2 expression in neuroblastoma cells beyond their individual effects. Mechanistic studies revealed that Ac5Neu5Ac supplementation increased intracellular CMP-Neu5Ac concentrations, thereby providing higher substrate levels for sialyltransferases. Furthermore, HDAC inhibitor treatment increased mRNA expression of the sialyltransferases GM3 synthase (ST3GAL5) and GD3 synthase (ST8SIA1) of which both are involved in GD2 biosynthesis. Our findings reveal that sialic acid analogues and HDAC inhibitors enhance GD2 expression and could potentially be employed to boost anti-GD2 targeted immunotherapy in neuroblastoma patients.",
author = "{van den Bijgaart}, {Renske J E} and Michiel Kroesen and Melissa Wassink and Brok, {Ingrid C} and Kers-Rebel, {Esther D} and Louis Boon and Torben Heise and {van Scherpenzeel}, Monique and Lefeber, {Dirk J} and Boltje, {Thomas J} and {den Brok}, {Martijn H} and Hoogerbrugge, {Peter M} and Christian B{\"u}ll and Adema, {Gosse J}",
note = "Published under license by The American Society for Biochemistry and Molecular Biology, Inc.",
year = "2019",
doi = "10.1074/jbc.RA118.002763",
language = "English",
pages = "4437--4449",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

}

RIS

TY - JOUR

T1 - Combined sialic acid and HDAC inhibitor treatment upregulates the neuroblastoma antigen GD2

AU - van den Bijgaart, Renske J E

AU - Kroesen, Michiel

AU - Wassink, Melissa

AU - Brok, Ingrid C

AU - Kers-Rebel, Esther D

AU - Boon, Louis

AU - Heise, Torben

AU - van Scherpenzeel, Monique

AU - Lefeber, Dirk J

AU - Boltje, Thomas J

AU - den Brok, Martijn H

AU - Hoogerbrugge, Peter M

AU - Büll, Christian

AU - Adema, Gosse J

N1 - Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2019

Y1 - 2019

N2 - Neuroblastoma cells highly express the disialoganglioside GD2, a tumor-associated carbohydrate antigen, which is only sparsely expressed on healthy tissue. GD2 is a primary target for the development of immunotherapy for neuroblastoma. Immunotherapy with monoclonal anti-GD2 antibodies has proven safety and efficacy in clinical trials and is included in the standard treatment for children with high-risk neuroblastoma. Strategies to modulate GD2 expression in neuroblastoma could further improve anti-GD2 targeted immunotherapy. Here, we report that the cellular sialylation pathway as well as epigenetic reprogramming strongly modulate GD2 expression in human and mouse neuroblastoma cell lines. Recognition of GD2 by the 14G2a antibody is sialic acid-dependent and was blocked with the fluorinated sialic acid mimetic Ac53FaxNeu5Ac. Interestingly, sialic acid supplementation using a cell-permeable sialic acid analogue (Ac5Neu5Ac) boosted GD2 expression without or with minor alterations in overall cell surface sialylation. Furthermore, sialic acid supplementation with Ac5Neu5Ac combined with various histone deacetylase (HDAC) inhibitors, including Vorinostat, enhanced GD2 expression in neuroblastoma cells beyond their individual effects. Mechanistic studies revealed that Ac5Neu5Ac supplementation increased intracellular CMP-Neu5Ac concentrations, thereby providing higher substrate levels for sialyltransferases. Furthermore, HDAC inhibitor treatment increased mRNA expression of the sialyltransferases GM3 synthase (ST3GAL5) and GD3 synthase (ST8SIA1) of which both are involved in GD2 biosynthesis. Our findings reveal that sialic acid analogues and HDAC inhibitors enhance GD2 expression and could potentially be employed to boost anti-GD2 targeted immunotherapy in neuroblastoma patients.

AB - Neuroblastoma cells highly express the disialoganglioside GD2, a tumor-associated carbohydrate antigen, which is only sparsely expressed on healthy tissue. GD2 is a primary target for the development of immunotherapy for neuroblastoma. Immunotherapy with monoclonal anti-GD2 antibodies has proven safety and efficacy in clinical trials and is included in the standard treatment for children with high-risk neuroblastoma. Strategies to modulate GD2 expression in neuroblastoma could further improve anti-GD2 targeted immunotherapy. Here, we report that the cellular sialylation pathway as well as epigenetic reprogramming strongly modulate GD2 expression in human and mouse neuroblastoma cell lines. Recognition of GD2 by the 14G2a antibody is sialic acid-dependent and was blocked with the fluorinated sialic acid mimetic Ac53FaxNeu5Ac. Interestingly, sialic acid supplementation using a cell-permeable sialic acid analogue (Ac5Neu5Ac) boosted GD2 expression without or with minor alterations in overall cell surface sialylation. Furthermore, sialic acid supplementation with Ac5Neu5Ac combined with various histone deacetylase (HDAC) inhibitors, including Vorinostat, enhanced GD2 expression in neuroblastoma cells beyond their individual effects. Mechanistic studies revealed that Ac5Neu5Ac supplementation increased intracellular CMP-Neu5Ac concentrations, thereby providing higher substrate levels for sialyltransferases. Furthermore, HDAC inhibitor treatment increased mRNA expression of the sialyltransferases GM3 synthase (ST3GAL5) and GD3 synthase (ST8SIA1) of which both are involved in GD2 biosynthesis. Our findings reveal that sialic acid analogues and HDAC inhibitors enhance GD2 expression and could potentially be employed to boost anti-GD2 targeted immunotherapy in neuroblastoma patients.

U2 - 10.1074/jbc.RA118.002763

DO - 10.1074/jbc.RA118.002763

M3 - Journal article

C2 - 30670592

SP - 4437

EP - 4449

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

ER -

ID: 212250178