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

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Liver metastasis of pancreatic Cancer: the hepatic microenvironment impacts differentiation and self-renewal capacity of pancreatic ductal epithelial cells. / Knaack, Hendrike; Lenk, Lennart; Philipp, Lisa-Marie; Miarka, Lauritz; Rahn, Sascha; Viol, Fabrice; Hauser, Charlotte; Egberts, Jan-Hendrik; Gundlach, Jan-Paul; Will, Olga; Tiwari, Sanjay; Mikulits, Wolfgang; Schumacher, Udo; Hengstler, Jan G; Sebens, Susanne.

in: ONCOTARGET, Jahrgang 9, Nr. 60, 03.08.2018, S. 31771-31786.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Knaack, H, Lenk, L, Philipp, L-M, Miarka, L, Rahn, S, Viol, F, Hauser, C, Egberts, J-H, Gundlach, J-P, Will, O, Tiwari, S, Mikulits, W, Schumacher, U, Hengstler, JG & Sebens, S 2018, 'Liver metastasis of pancreatic Cancer: the hepatic microenvironment impacts differentiation and self-renewal capacity of pancreatic ductal epithelial cells', ONCOTARGET, Jg. 9, Nr. 60, S. 31771-31786. https://doi.org/10.18632/oncotarget.25884

APA

Knaack, H., Lenk, L., Philipp, L-M., Miarka, L., Rahn, S., Viol, F., Hauser, C., Egberts, J-H., Gundlach, J-P., Will, O., Tiwari, S., Mikulits, W., Schumacher, U., Hengstler, J. G., & Sebens, S. (2018). Liver metastasis of pancreatic Cancer: the hepatic microenvironment impacts differentiation and self-renewal capacity of pancreatic ductal epithelial cells. ONCOTARGET, 9(60), 31771-31786. https://doi.org/10.18632/oncotarget.25884

Vancouver

Knaack H, Lenk L, Philipp L-M, Miarka L, Rahn S, Viol F et al. Liver metastasis of pancreatic Cancer: the hepatic microenvironment impacts differentiation and self-renewal capacity of pancreatic ductal epithelial cells. ONCOTARGET. 2018 Aug 3;9(60):31771-31786. https://doi.org/10.18632/oncotarget.25884

Bibtex

@article{1a6d10fff2304de69870919361058255,
title = "Liver metastasis of pancreatic Cancer: the hepatic microenvironment impacts differentiation and self-renewal capacity of pancreatic ductal epithelial cells",
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.",
keywords = "Journal Article",
author = "Hendrike Knaack and Lennart Lenk and Lisa-Marie Philipp and Lauritz Miarka and Sascha Rahn and Fabrice Viol and Charlotte Hauser and Jan-Hendrik Egberts and Jan-Paul Gundlach and Olga Will and Sanjay Tiwari and Wolfgang Mikulits and Udo Schumacher and Hengstler, {Jan G} and Susanne Sebens",
year = "2018",
month = aug,
day = "3",
doi = "10.18632/oncotarget.25884",
language = "English",
volume = "9",
pages = "31771--31786",
journal = "ONCOTARGET",
issn = "1949-2553",
publisher = "IMPACT JOURNALS LLC",
number = "60",

}

RIS

TY - JOUR

T1 - Liver metastasis of pancreatic Cancer: the hepatic microenvironment impacts differentiation and self-renewal capacity of pancreatic ductal epithelial cells

AU - Knaack, Hendrike

AU - Lenk, Lennart

AU - Philipp, Lisa-Marie

AU - Miarka, Lauritz

AU - Rahn, Sascha

AU - Viol, Fabrice

AU - Hauser, Charlotte

AU - Egberts, Jan-Hendrik

AU - Gundlach, Jan-Paul

AU - Will, Olga

AU - Tiwari, Sanjay

AU - Mikulits, Wolfgang

AU - Schumacher, Udo

AU - Hengstler, Jan G

AU - Sebens, Susanne

PY - 2018/8/3

Y1 - 2018/8/3

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.18632/oncotarget.25884

DO - 10.18632/oncotarget.25884

M3 - SCORING: Journal article

C2 - 30167093

VL - 9

SP - 31771

EP - 31786

JO - ONCOTARGET

JF - ONCOTARGET

SN - 1949-2553

IS - 60

ER -