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

Oncotarget
Hendrike KnaackSusanne Sebens

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 fo...Continue Reading

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Citations

Jul 3, 2019·Clinical and Translational Medicine·Tovah WilliamsonHossein Sendi
Jul 19, 2019·Biological Chemistry·Dieter Häussinger, Claus Kordes
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Dec 19, 2021·Journal of Gastrointestinal Cancer·Yunus Akkoc, Devrim Gozuacik

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Methods Mentioned

BETA
PDECs
xenograft

Software Mentioned

SigmaPlot

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