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Shiga toxin glycosphingolipid receptor expression and toxin susceptibility of human pancreatic ductal adenocarcinomas of differing origin and differentiation

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Shiga toxin glycosphingolipid receptor expression and toxin susceptibility of human pancreatic ductal adenocarcinomas of differing origin and differentiation. / Storck, Wiebke; Meisen, Iris; Gianmoena, Kathrin; Pläger, Ina; Kouzel, Ivan U; Bielaszewska, Martina; Haier, Jörg; Mormann, Michael; Humpf, Hans-Ulrich; Karch, Helge; Müthing, Johannes.

In: BIOL CHEM, Vol. 393, No. 8, 08.2012, p. 785-99.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Storck, W, Meisen, I, Gianmoena, K, Pläger, I, Kouzel, IU, Bielaszewska, M, Haier, J, Mormann, M, Humpf, H-U, Karch, H & Müthing, J 2012, 'Shiga toxin glycosphingolipid receptor expression and toxin susceptibility of human pancreatic ductal adenocarcinomas of differing origin and differentiation', BIOL CHEM, vol. 393, no. 8, pp. 785-99. https://doi.org/10.1515/hsz-2012-0165

APA

Storck, W., Meisen, I., Gianmoena, K., Pläger, I., Kouzel, I. U., Bielaszewska, M., Haier, J., Mormann, M., Humpf, H-U., Karch, H., & Müthing, J. (2012). Shiga toxin glycosphingolipid receptor expression and toxin susceptibility of human pancreatic ductal adenocarcinomas of differing origin and differentiation. BIOL CHEM, 393(8), 785-99. https://doi.org/10.1515/hsz-2012-0165

Vancouver

Storck W, Meisen I, Gianmoena K, Pläger I, Kouzel IU, Bielaszewska M et al. Shiga toxin glycosphingolipid receptor expression and toxin susceptibility of human pancreatic ductal adenocarcinomas of differing origin and differentiation. BIOL CHEM. 2012 Aug;393(8):785-99. https://doi.org/10.1515/hsz-2012-0165

Bibtex

@article{15ed3cc6dda741deb616aecef629dc92,
title = "Shiga toxin glycosphingolipid receptor expression and toxin susceptibility of human pancreatic ductal adenocarcinomas of differing origin and differentiation",
abstract = "Shiga toxins (Stxs) are composed of an enzymatically active A subunit (StxA) and a pentameric B subunit (StxB) that preferentially binds to the glycosphingolipid (GSL) globo\xadtriaosylceramide (Gb3Cer/CD77) and to a reduced extent to globotetraosylceramide (Gb4Cer). The identification of Gb3Cer as a tumor-associated GSL in human pancreatic cancer prompted us to investigate the expression of Gb3Cer and Gb4Cer in 15 human pancreatic ductal adenocarcinoma cell lines derived from primary tumors and liver, ascites, and lymph node metastases. Thin-layer chromatography overlay assays revealed the occurrence of Gb3Cer in all and of Gb4Cer in the majority of cell lines, which largely correlated with transcriptional expression analysis of Gb3Cer and Gb4Cer synthases. Prominent Gb3Cer and Gb4Cer lipoform heterogeneity was based on ceramides carrying predominantly C16:0 and C24:0/C24:1 fatty acids. Stx2-mediated cell injury ranged from extremely high sensitivity (CD(50) of 0.94 pg/ml) to high refractiveness (CD(50) of 5.8 μg/ml) and to virtual resistance portrayed by non-determinable CD(50) values even at the highest Stx2 concentration (10 μg/ml) applied. Importantly, Stx2-mediated cytotoxicity did not correlate with Gb3Cer expression (the preferential Stx receptor), suggesting that the GSL receptor content does not primarily determine cell sensitivity and that other, yet to be delineated, cellular factors might influence the responsiveness of cancer cells.",
keywords = "Adenocarcinoma, Ascites, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Cell Survival, Gene Expression Regulation, Neoplastic, Globosides, Humans, Liver Neoplasms, Lymph Nodes, Shiga Toxin 2, Shiga-Toxigenic Escherichia coli, Trihexosylceramides",
author = "Wiebke Storck and Iris Meisen and Kathrin Gianmoena and Ina Pl{\"a}ger and Kouzel, {Ivan U} and Martina Bielaszewska and J{\"o}rg Haier and Michael Mormann and Hans-Ulrich Humpf and Helge Karch and Johannes M{\"u}thing",
year = "2012",
month = aug,
doi = "10.1515/hsz-2012-0165",
language = "English",
volume = "393",
pages = "785--99",
journal = "BIOL CHEM",
issn = "1431-6730",
publisher = "Walter de Gruyter GmbH & Co. KG",
number = "8",

}

RIS

TY - JOUR

T1 - Shiga toxin glycosphingolipid receptor expression and toxin susceptibility of human pancreatic ductal adenocarcinomas of differing origin and differentiation

AU - Storck, Wiebke

AU - Meisen, Iris

AU - Gianmoena, Kathrin

AU - Pläger, Ina

AU - Kouzel, Ivan U

AU - Bielaszewska, Martina

AU - Haier, Jörg

AU - Mormann, Michael

AU - Humpf, Hans-Ulrich

AU - Karch, Helge

AU - Müthing, Johannes

PY - 2012/8

Y1 - 2012/8

N2 - Shiga toxins (Stxs) are composed of an enzymatically active A subunit (StxA) and a pentameric B subunit (StxB) that preferentially binds to the glycosphingolipid (GSL) globo\xadtriaosylceramide (Gb3Cer/CD77) and to a reduced extent to globotetraosylceramide (Gb4Cer). The identification of Gb3Cer as a tumor-associated GSL in human pancreatic cancer prompted us to investigate the expression of Gb3Cer and Gb4Cer in 15 human pancreatic ductal adenocarcinoma cell lines derived from primary tumors and liver, ascites, and lymph node metastases. Thin-layer chromatography overlay assays revealed the occurrence of Gb3Cer in all and of Gb4Cer in the majority of cell lines, which largely correlated with transcriptional expression analysis of Gb3Cer and Gb4Cer synthases. Prominent Gb3Cer and Gb4Cer lipoform heterogeneity was based on ceramides carrying predominantly C16:0 and C24:0/C24:1 fatty acids. Stx2-mediated cell injury ranged from extremely high sensitivity (CD(50) of 0.94 pg/ml) to high refractiveness (CD(50) of 5.8 μg/ml) and to virtual resistance portrayed by non-determinable CD(50) values even at the highest Stx2 concentration (10 μg/ml) applied. Importantly, Stx2-mediated cytotoxicity did not correlate with Gb3Cer expression (the preferential Stx receptor), suggesting that the GSL receptor content does not primarily determine cell sensitivity and that other, yet to be delineated, cellular factors might influence the responsiveness of cancer cells.

AB - Shiga toxins (Stxs) are composed of an enzymatically active A subunit (StxA) and a pentameric B subunit (StxB) that preferentially binds to the glycosphingolipid (GSL) globo\xadtriaosylceramide (Gb3Cer/CD77) and to a reduced extent to globotetraosylceramide (Gb4Cer). The identification of Gb3Cer as a tumor-associated GSL in human pancreatic cancer prompted us to investigate the expression of Gb3Cer and Gb4Cer in 15 human pancreatic ductal adenocarcinoma cell lines derived from primary tumors and liver, ascites, and lymph node metastases. Thin-layer chromatography overlay assays revealed the occurrence of Gb3Cer in all and of Gb4Cer in the majority of cell lines, which largely correlated with transcriptional expression analysis of Gb3Cer and Gb4Cer synthases. Prominent Gb3Cer and Gb4Cer lipoform heterogeneity was based on ceramides carrying predominantly C16:0 and C24:0/C24:1 fatty acids. Stx2-mediated cell injury ranged from extremely high sensitivity (CD(50) of 0.94 pg/ml) to high refractiveness (CD(50) of 5.8 μg/ml) and to virtual resistance portrayed by non-determinable CD(50) values even at the highest Stx2 concentration (10 μg/ml) applied. Importantly, Stx2-mediated cytotoxicity did not correlate with Gb3Cer expression (the preferential Stx receptor), suggesting that the GSL receptor content does not primarily determine cell sensitivity and that other, yet to be delineated, cellular factors might influence the responsiveness of cancer cells.

KW - Adenocarcinoma

KW - Ascites

KW - Carcinoma, Pancreatic Ductal

KW - Cell Line, Tumor

KW - Cell Survival

KW - Gene Expression Regulation, Neoplastic

KW - Globosides

KW - Humans

KW - Liver Neoplasms

KW - Lymph Nodes

KW - Shiga Toxin 2

KW - Shiga-Toxigenic Escherichia coli

KW - Trihexosylceramides

U2 - 10.1515/hsz-2012-0165

DO - 10.1515/hsz-2012-0165

M3 - SCORING: Journal article

C2 - 22944681

VL - 393

SP - 785

EP - 799

JO - BIOL CHEM

JF - BIOL CHEM

SN - 1431-6730

IS - 8

ER -