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Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells

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Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells. / Rahn, Sascha; Zimmermann, Vivien; Viol, Fabrice; Knaack, Hendrike; Stemmer, Kerstin; Peters, Lena; Lenk, Lennart; Ungefroren, Hendrik; Saur, Dieter; Schäfer, Heiner; Helm, Ole; Sebens, Susanne.

In: CANCER LETT, Vol. 415, 28.02.2018, p. 129-150.

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

Harvard

Rahn, S, Zimmermann, V, Viol, F, Knaack, H, Stemmer, K, Peters, L, Lenk, L, Ungefroren, H, Saur, D, Schäfer, H, Helm, O & Sebens, S 2018, 'Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells', CANCER LETT, vol. 415, pp. 129-150. https://doi.org/10.1016/j.canlet.2017.12.004

APA

Rahn, S., Zimmermann, V., Viol, F., Knaack, H., Stemmer, K., Peters, L., Lenk, L., Ungefroren, H., Saur, D., Schäfer, H., Helm, O., & Sebens, S. (2018). Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells. CANCER LETT, 415, 129-150. https://doi.org/10.1016/j.canlet.2017.12.004

Vancouver

Rahn S, Zimmermann V, Viol F, Knaack H, Stemmer K, Peters L et al. Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells. CANCER LETT. 2018 Feb 28;415:129-150. https://doi.org/10.1016/j.canlet.2017.12.004

Bibtex

@article{e235d4c38110493e96b73bf123d7e7cf,
title = "Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells",
abstract = "Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia and a risk to develop pancreatic ductal adenocarcinoma (PDAC), one of the most fatal malignancies. Cancer stem cells (CSC) are essential for initiation and maintenance of tumors, and acquisition of CSC-features is linked to epithelial-mesenchymal-transition (EMT). The present study investigated whether hyperglycemia promotes EMT and CSC-features in premalignant and malignant pancreatic ductal epithelial cells (PDEC). Under normoglycemia (5 mM d-glucose), Panc1 PDAC cells but not premalignant H6c7-kras cells exhibited a mesenchymal phenotype along with pronounced colony formation. While hyperglycemia (25 mM d-glucose) did not impact the mesenchymal phenotype of Panc1 cells, CSC-properties were aggravated exemplified by increased Nanog expression and Nanog-dependent formation of holo- and meroclones. In H6c7-kras cells, high glucose increased secretion of Transforming-Growth-Factor-beta1 (TGF-β1) as well as TGF-β1 signaling, and in a TGF-β1-dependent manner reduced E-cadherin expression, increased Nestin expression and number of meroclones. Finally, reduced E-cadherin expression was detected in pancreatic ducts of hyperglycemic but not normoglycemic mice. These data suggest that hyperglycemia promotes the acquisition of mesenchymal and CSC-properties in PDEC by activating TGF-β signaling and might explain how T2DM facilitates pancreatic tumorigenesis.",
keywords = "Animals, Cell Line, Cell Line, Tumor, Diabetes Mellitus, Type 2, Epithelial Cells, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Glucose, Humans, Hyperglycemia, Male, Mice, Inbred C57BL, Neoplastic Stem Cells, Pancreatic Ducts, Pancreatic Neoplasms, Risk Factors, Transforming Growth Factor beta1, Journal Article, Research Support, Non-U.S. Gov't",
author = "Sascha Rahn and Vivien Zimmermann and Fabrice Viol and Hendrike Knaack and Kerstin Stemmer and Lena Peters and Lennart Lenk and Hendrik Ungefroren and Dieter Saur and Heiner Sch{\"a}fer and Ole Helm and Susanne Sebens",
note = "Copyright {\textcopyright} 2017 Elsevier B.V. All rights reserved.",
year = "2018",
month = feb,
day = "28",
doi = "10.1016/j.canlet.2017.12.004",
language = "English",
volume = "415",
pages = "129--150",
journal = "CANCER LETT",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells

AU - Rahn, Sascha

AU - Zimmermann, Vivien

AU - Viol, Fabrice

AU - Knaack, Hendrike

AU - Stemmer, Kerstin

AU - Peters, Lena

AU - Lenk, Lennart

AU - Ungefroren, Hendrik

AU - Saur, Dieter

AU - Schäfer, Heiner

AU - Helm, Ole

AU - Sebens, Susanne

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2018/2/28

Y1 - 2018/2/28

N2 - Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia and a risk to develop pancreatic ductal adenocarcinoma (PDAC), one of the most fatal malignancies. Cancer stem cells (CSC) are essential for initiation and maintenance of tumors, and acquisition of CSC-features is linked to epithelial-mesenchymal-transition (EMT). The present study investigated whether hyperglycemia promotes EMT and CSC-features in premalignant and malignant pancreatic ductal epithelial cells (PDEC). Under normoglycemia (5 mM d-glucose), Panc1 PDAC cells but not premalignant H6c7-kras cells exhibited a mesenchymal phenotype along with pronounced colony formation. While hyperglycemia (25 mM d-glucose) did not impact the mesenchymal phenotype of Panc1 cells, CSC-properties were aggravated exemplified by increased Nanog expression and Nanog-dependent formation of holo- and meroclones. In H6c7-kras cells, high glucose increased secretion of Transforming-Growth-Factor-beta1 (TGF-β1) as well as TGF-β1 signaling, and in a TGF-β1-dependent manner reduced E-cadherin expression, increased Nestin expression and number of meroclones. Finally, reduced E-cadherin expression was detected in pancreatic ducts of hyperglycemic but not normoglycemic mice. These data suggest that hyperglycemia promotes the acquisition of mesenchymal and CSC-properties in PDEC by activating TGF-β signaling and might explain how T2DM facilitates pancreatic tumorigenesis.

AB - Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia and a risk to develop pancreatic ductal adenocarcinoma (PDAC), one of the most fatal malignancies. Cancer stem cells (CSC) are essential for initiation and maintenance of tumors, and acquisition of CSC-features is linked to epithelial-mesenchymal-transition (EMT). The present study investigated whether hyperglycemia promotes EMT and CSC-features in premalignant and malignant pancreatic ductal epithelial cells (PDEC). Under normoglycemia (5 mM d-glucose), Panc1 PDAC cells but not premalignant H6c7-kras cells exhibited a mesenchymal phenotype along with pronounced colony formation. While hyperglycemia (25 mM d-glucose) did not impact the mesenchymal phenotype of Panc1 cells, CSC-properties were aggravated exemplified by increased Nanog expression and Nanog-dependent formation of holo- and meroclones. In H6c7-kras cells, high glucose increased secretion of Transforming-Growth-Factor-beta1 (TGF-β1) as well as TGF-β1 signaling, and in a TGF-β1-dependent manner reduced E-cadherin expression, increased Nestin expression and number of meroclones. Finally, reduced E-cadherin expression was detected in pancreatic ducts of hyperglycemic but not normoglycemic mice. These data suggest that hyperglycemia promotes the acquisition of mesenchymal and CSC-properties in PDEC by activating TGF-β signaling and might explain how T2DM facilitates pancreatic tumorigenesis.

KW - Animals

KW - Cell Line

KW - Cell Line, Tumor

KW - Diabetes Mellitus, Type 2

KW - Epithelial Cells

KW - Epithelial-Mesenchymal Transition

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Glucose

KW - Humans

KW - Hyperglycemia

KW - Male

KW - Mice, Inbred C57BL

KW - Neoplastic Stem Cells

KW - Pancreatic Ducts

KW - Pancreatic Neoplasms

KW - Risk Factors

KW - Transforming Growth Factor beta1

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.canlet.2017.12.004

DO - 10.1016/j.canlet.2017.12.004

M3 - SCORING: Journal article

C2 - 29222037

VL - 415

SP - 129

EP - 150

JO - CANCER LETT

JF - CANCER LETT

SN - 0304-3835

ER -