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Shiga toxin receptor Gb3Cer/CD77

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Shiga toxin receptor Gb3Cer/CD77 : tumor-association and promising therapeutic target in pancreas and colon cancer. / Distler, Ute; Souady, Jamal; Hülsewig, Marcel; Drmić-Hofman, Irena; Haier, Jörg; Friedrich, Alexander W; Karch, Helge; Senninger, Norbert; Dreisewerd, Klaus; Berkenkamp, Stefan; Schmidt, M Alexander; Peter-Katalinić, Jasna; Müthing, Johannes.

In: PLOS ONE, Vol. 4, No. 8, 2009, p. e6813.

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

Harvard

Distler, U, Souady, J, Hülsewig, M, Drmić-Hofman, I, Haier, J, Friedrich, AW, Karch, H, Senninger, N, Dreisewerd, K, Berkenkamp, S, Schmidt, MA, Peter-Katalinić, J & Müthing, J 2009, 'Shiga toxin receptor Gb3Cer/CD77: tumor-association and promising therapeutic target in pancreas and colon cancer', PLOS ONE, vol. 4, no. 8, pp. e6813. https://doi.org/10.1371/journal.pone.0006813

APA

Distler, U., Souady, J., Hülsewig, M., Drmić-Hofman, I., Haier, J., Friedrich, A. W., Karch, H., Senninger, N., Dreisewerd, K., Berkenkamp, S., Schmidt, M. A., Peter-Katalinić, J., & Müthing, J. (2009). Shiga toxin receptor Gb3Cer/CD77: tumor-association and promising therapeutic target in pancreas and colon cancer. PLOS ONE, 4(8), e6813. https://doi.org/10.1371/journal.pone.0006813

Vancouver

Distler U, Souady J, Hülsewig M, Drmić-Hofman I, Haier J, Friedrich AW et al. Shiga toxin receptor Gb3Cer/CD77: tumor-association and promising therapeutic target in pancreas and colon cancer. PLOS ONE. 2009;4(8):e6813. https://doi.org/10.1371/journal.pone.0006813

Bibtex

@article{c7863b1376354c7c872706f7b5b19ad2,
title = "Shiga toxin receptor Gb3Cer/CD77: tumor-association and promising therapeutic target in pancreas and colon cancer",
abstract = "BACKGROUND: Despite progress in adjuvant chemotherapy in the recent decades, pancreatic and colon cancers remain common causes of death worldwide. Bacterial toxins, which specifically bind to cell surface-exposed glycosphingolipids, are a potential novel therapy. We determined the expression of globotriaosylceramide (Gb3Cer/CD77), the Shiga toxin receptor, in human pancreatic and colon adenocarcinomas.METHODOLOGY/PRINCIPAL FINDINGS: Tissue lipid extracts of matched pairs of cancerous and adjacent normal tissue from 21 pancreatic and 16 colon cancer patients were investigated with thin-layer chromatography overlay assay combined with a novel mass spectrometry approach. Gb3Cer/CD77 was localized by immunofluorescence microscopy of cryosections from malignant and corresponding healthy tissue samples. 62% of pancreatic and 81% of colon adenocarcinomas showed increased Gb3Cer/CD77 expression, whereas 38% and 19% of malignant pancreas and colon tissue, respectively, did not, indicating an association of this marker with neoplastic transformation. Also, Gb3Cer/CD77 was associated with poor differentiation (G>2) in pancreatic cancer (P = 0.039). Mass spectrometric analysis evidenced enhanced expression of Gb3Cer/CD77 with long (C24) and short chain fatty acids (C16) in malignant tissues and pointed to the presence of hydroxylated fatty acid lipoforms, which are proposed to be important for receptor targeting. They could be detected in 86% of pancreatic and about 19% of colon adenocarcinomas. Immunohistology of tissue cryosections indicated tumor-association of these receptors.CONCLUSIONS/SIGNIFICANCE: Enhanced expression of Gb3Cer/CD77 in most pancreatic and colon adenocarcinomas prompts consideration of Shiga toxin, its B-subunit or B-subunit-derivatives as novel therapeutic strategies for the treatment of these challenging malignancies.",
keywords = "Adenocarcinoma, Carbohydrate Sequence, Chromatography, Thin Layer, Colonic Neoplasms, Humans, Immunohistochemistry, Molecular Sequence Data, Pancreatic Neoplasms, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Trihexosylceramides",
author = "Ute Distler and Jamal Souady and Marcel H{\"u}lsewig and Irena Drmi{\'c}-Hofman and J{\"o}rg Haier and Friedrich, {Alexander W} and Helge Karch and Norbert Senninger and Klaus Dreisewerd and Stefan Berkenkamp and Schmidt, {M Alexander} and Jasna Peter-Katalini{\'c} and Johannes M{\"u}thing",
year = "2009",
doi = "10.1371/journal.pone.0006813",
language = "English",
volume = "4",
pages = "e6813",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

RIS

TY - JOUR

T1 - Shiga toxin receptor Gb3Cer/CD77

T2 - tumor-association and promising therapeutic target in pancreas and colon cancer

AU - Distler, Ute

AU - Souady, Jamal

AU - Hülsewig, Marcel

AU - Drmić-Hofman, Irena

AU - Haier, Jörg

AU - Friedrich, Alexander W

AU - Karch, Helge

AU - Senninger, Norbert

AU - Dreisewerd, Klaus

AU - Berkenkamp, Stefan

AU - Schmidt, M Alexander

AU - Peter-Katalinić, Jasna

AU - Müthing, Johannes

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Despite progress in adjuvant chemotherapy in the recent decades, pancreatic and colon cancers remain common causes of death worldwide. Bacterial toxins, which specifically bind to cell surface-exposed glycosphingolipids, are a potential novel therapy. We determined the expression of globotriaosylceramide (Gb3Cer/CD77), the Shiga toxin receptor, in human pancreatic and colon adenocarcinomas.METHODOLOGY/PRINCIPAL FINDINGS: Tissue lipid extracts of matched pairs of cancerous and adjacent normal tissue from 21 pancreatic and 16 colon cancer patients were investigated with thin-layer chromatography overlay assay combined with a novel mass spectrometry approach. Gb3Cer/CD77 was localized by immunofluorescence microscopy of cryosections from malignant and corresponding healthy tissue samples. 62% of pancreatic and 81% of colon adenocarcinomas showed increased Gb3Cer/CD77 expression, whereas 38% and 19% of malignant pancreas and colon tissue, respectively, did not, indicating an association of this marker with neoplastic transformation. Also, Gb3Cer/CD77 was associated with poor differentiation (G>2) in pancreatic cancer (P = 0.039). Mass spectrometric analysis evidenced enhanced expression of Gb3Cer/CD77 with long (C24) and short chain fatty acids (C16) in malignant tissues and pointed to the presence of hydroxylated fatty acid lipoforms, which are proposed to be important for receptor targeting. They could be detected in 86% of pancreatic and about 19% of colon adenocarcinomas. Immunohistology of tissue cryosections indicated tumor-association of these receptors.CONCLUSIONS/SIGNIFICANCE: Enhanced expression of Gb3Cer/CD77 in most pancreatic and colon adenocarcinomas prompts consideration of Shiga toxin, its B-subunit or B-subunit-derivatives as novel therapeutic strategies for the treatment of these challenging malignancies.

AB - BACKGROUND: Despite progress in adjuvant chemotherapy in the recent decades, pancreatic and colon cancers remain common causes of death worldwide. Bacterial toxins, which specifically bind to cell surface-exposed glycosphingolipids, are a potential novel therapy. We determined the expression of globotriaosylceramide (Gb3Cer/CD77), the Shiga toxin receptor, in human pancreatic and colon adenocarcinomas.METHODOLOGY/PRINCIPAL FINDINGS: Tissue lipid extracts of matched pairs of cancerous and adjacent normal tissue from 21 pancreatic and 16 colon cancer patients were investigated with thin-layer chromatography overlay assay combined with a novel mass spectrometry approach. Gb3Cer/CD77 was localized by immunofluorescence microscopy of cryosections from malignant and corresponding healthy tissue samples. 62% of pancreatic and 81% of colon adenocarcinomas showed increased Gb3Cer/CD77 expression, whereas 38% and 19% of malignant pancreas and colon tissue, respectively, did not, indicating an association of this marker with neoplastic transformation. Also, Gb3Cer/CD77 was associated with poor differentiation (G>2) in pancreatic cancer (P = 0.039). Mass spectrometric analysis evidenced enhanced expression of Gb3Cer/CD77 with long (C24) and short chain fatty acids (C16) in malignant tissues and pointed to the presence of hydroxylated fatty acid lipoforms, which are proposed to be important for receptor targeting. They could be detected in 86% of pancreatic and about 19% of colon adenocarcinomas. Immunohistology of tissue cryosections indicated tumor-association of these receptors.CONCLUSIONS/SIGNIFICANCE: Enhanced expression of Gb3Cer/CD77 in most pancreatic and colon adenocarcinomas prompts consideration of Shiga toxin, its B-subunit or B-subunit-derivatives as novel therapeutic strategies for the treatment of these challenging malignancies.

KW - Adenocarcinoma

KW - Carbohydrate Sequence

KW - Chromatography, Thin Layer

KW - Colonic Neoplasms

KW - Humans

KW - Immunohistochemistry

KW - Molecular Sequence Data

KW - Pancreatic Neoplasms

KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

KW - Trihexosylceramides

U2 - 10.1371/journal.pone.0006813

DO - 10.1371/journal.pone.0006813

M3 - SCORING: Journal article

C2 - 19714252

VL - 4

SP - e6813

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 8

ER -