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, Jahrgang 393, Nr. 8, 08.2012, S. 785-99.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -