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798 results on '"Udo Schumacher"'

152. Warum PROMETHEUS?

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl Wesker

Published
2018

153. 3 Blut

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

156. Liver metastasis of pancreatic cancer: the hepatic microenvironment impacts differentiation and self-renewal capacity of pancreatic ductal epithelial cells

Author

Jan-Hendrik Egberts, Olga Will, Sascha Rahn, Jan-Paul Gundlach, Lauritz Miarka, Jan G. Hengstler, Fabrice Viol, Hendrike Knaack, Lisa-Marie Philipp, Charlotte Hauser, Sanjay Tiwari, Lennart Lenk, Wolfgang Mikulits, Susanne Sebens, and Udo Schumacher

Subjects
0301 basic medicine, cancer stem cell, Mesenchymal stem cell, EMT, pancreatic ductal adenocarcinoma, Biology, Nestin, medicine.disease, epithelial-mesenchymal-transition, Metastasis, 03 medical and health sciences, 030104 developmental biology, hepatic microenvironment, Oncology, Cancer stem cell, Pancreatic cancer, medicine, Hepatic stellate cell, Cancer research, Tumor necrosis factor alpha, Epithelial–mesenchymal transition, Research Paper
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at advanced stages with the liver as the main site of metastases. The hepatic microenvironment has been shown to determine outgrowth of liver metastases. Cancer stem cells (CSCs) are essential for initiation and maintenance of tumors and acquisition of CSC-properties has been linked to Epithelial-Mesenchymal-Transition. Thus, this study aimed at elucidating whether and how the hepatic microenvironment impacts stemness and differentiation of disseminated pancreatic ductal epithelial cells (PDECs). Culture of premalignant H6c7-kras and malignant Panc1 PDECs together with hepatocytes and hepatic stellate cells (HSC) promoted self-renewal capacity of both PDEC lines. This was indicated by higher colony formation compared to cells cocultured with hepatocytes and hepatic myofibroblasts. Different Panc1 colony types derived from an HSC-enriched coculture were expanded and characterized revealing that holoclones exhibited an enhanced colony formation ability, elevated and exclusive expression of the CSC-marker Nestin and a more pronounced mesenchymal phenotype compared to paraclones. Moreover, Panc1 holoclone cells showed an increased tumorigenic potential in vivo leading to formation of undifferentiated tumors in 7/10 animals, while inoculation of paraclone cells only led to formation of tumors in 2/10 animals being smaller in number and size. Holoclone tumors were characterized by elevated expression of mesenchymal markers, complete loss of E-cadherin expression and high expression of Nestin. Finally, Etanercept-mediated TNF-α blocking partly reversed the mesenchymal CSC-phenotype of Panc1 holoclone cells. Overall, these data provide evidence that the hepatic microenvironment determines stemness and differentiation of PDECs, thereby substantially contributing to liver metastases of PDAC.

Published
2018

158. 7 Schnittbilder

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl Wesker

Published
2018

160. 3 Vegetatives Nervensystem

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl Wesker

Published
2018

161. 4 Lymphatisches System

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

164. Literaturverzeichnis

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl Wesker

Published
2018

168. 9 Cerebellum

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl Wesker

Published
2018

169. 9 Endokrines System

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

170. 6 Verdauungssystem

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

173. 10 Vegetatives Nervensystem

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

174. Sachverzeichnis

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl Wesker

Published
2018

176. 1 Übersicht

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl Wesker

Published
2018

177. 1 Überblick und Zwerchfell

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

179. 1 Glossar

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl Wesker

Published
2018

184. PROMETHEUS Innere Organe

Author

Karl Wesker, Michael Schünke, Udo Schumacher, Erik Schulte, and Markus Voll

Published
2018

185. 6 Topografische Anatomie

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

188. 5 Muskeln

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

189. 6 Topografie

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl Wesker

Published
2018

190. 6 Gefäße

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

192. 2 Kreislaufsystem

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

194. 2 Synopsen

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl Wesker

Published
2018

196. 8 Genitalsystem

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

197. 7 Harnsystem

Author

Michael Schünke, Erik Schulte, Udo Schumacher, Markus Voll, and Karl H. Wesker

Published
2018

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