Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
DOI
PMC
 |
|
Open Access Green as soon as Postprint is submitted to ZB.
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 (2018)
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 Pancl 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-betal (TGF-beta 1) as well as TGF-beta 1 signaling, and in a TGF-beta 1-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-beta signaling and might explain how T2DM facilitates pancreatic tumorigenesis. (C) 2017 Elsevier B.V. All rights reserved.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Pancreatic Cancer ; Diabetes ; Glucose ; Cancer Stemness ; Emt; High Glucose Promotes; Tgf-beta; Signaling Pathway; Up-regulation; Cardiac Fibroblasts; Calorie Restriction; Carcinoma-cells; Mouse Model; K-ras; Adenocarcinoma
ISSN (print) / ISBN
0304-3835
e-ISSN
0304-3835
Journal
Cancer Letters
Quellenangaben
Volume: 415,
Pages: 129-150
Publisher
Elsevier
Publishing Place
Clare
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)