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Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer

In highly aggressive malignancies like pancreatic cancer (PC), patient-derived tumor models can serve as disease-relevant models to understand disease-related biology as well as to guide clinical decision-making. In this study, we describe a two-step protocol allowing systematic establishment of pat...

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Autores principales: Ehrenberg, Karl Roland, Gao, Jianpeng, Oppel, Felix, Frank, Stephanie, Kang, Na, Kindinger, Tim, Dieter, Sebastian M., Herbst, Friederike, Möhrmann, Lino, Dubash, Taronish D., Schulz, Erik R., Strakerjahn, Hendrik, Giessler, Klara M., Weber, Sarah, Oberlack, Ava, Rief, Eva-Maria, Strobel, Oliver, Bergmann, Frank, Lasitschka, Felix, Weitz, Jürgen, Glimm, Hanno, Ball, Claudia R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406729/
https://www.ncbi.nlm.nih.gov/pubmed/30744205
http://dx.doi.org/10.3390/cells8020142
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author Ehrenberg, Karl Roland
Gao, Jianpeng
Oppel, Felix
Frank, Stephanie
Kang, Na
Kindinger, Tim
Dieter, Sebastian M.
Herbst, Friederike
Möhrmann, Lino
Dubash, Taronish D.
Schulz, Erik R.
Strakerjahn, Hendrik
Giessler, Klara M.
Weber, Sarah
Oberlack, Ava
Rief, Eva-Maria
Strobel, Oliver
Bergmann, Frank
Lasitschka, Felix
Weitz, Jürgen
Glimm, Hanno
Ball, Claudia R.
author_facet Ehrenberg, Karl Roland
Gao, Jianpeng
Oppel, Felix
Frank, Stephanie
Kang, Na
Kindinger, Tim
Dieter, Sebastian M.
Herbst, Friederike
Möhrmann, Lino
Dubash, Taronish D.
Schulz, Erik R.
Strakerjahn, Hendrik
Giessler, Klara M.
Weber, Sarah
Oberlack, Ava
Rief, Eva-Maria
Strobel, Oliver
Bergmann, Frank
Lasitschka, Felix
Weitz, Jürgen
Glimm, Hanno
Ball, Claudia R.
author_sort Ehrenberg, Karl Roland
collection PubMed
description In highly aggressive malignancies like pancreatic cancer (PC), patient-derived tumor models can serve as disease-relevant models to understand disease-related biology as well as to guide clinical decision-making. In this study, we describe a two-step protocol allowing systematic establishment of patient-derived primary cultures from PC patient tumors. Initial xenotransplantation of surgically resected patient tumors (n = 134) into immunodeficient mice allows for efficient in vivo expansion of vital tumor cells and successful tumor expansion in 38% of patient tumors (51/134). Expansion xenografts closely recapitulate the histoarchitecture of their matching patients’ primary tumors. Digestion of xenograft tumors and subsequent in vitro cultivation resulted in the successful generation of semi-adherent PC cultures of pure epithelial cell origin in 43.1% of the cases. The established primary cultures include diverse pathological types of PC: Pancreatic ductal adenocarcinoma (86.3%, 19/22), adenosquamous carcinoma (9.1%, 2/22) and ductal adenocarcinoma with oncocytic IPMN (4.5%, 1/22). We here provide a protocol to establish quality-controlled PC patient-derived primary cell cultures from heterogeneous PC patient tumors. In vitro preclinical models provide the basis for the identification and preclinical assessment of novel therapeutic opportunities targeting pancreatic cancer.
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spelling pubmed-64067292019-03-19 Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer Ehrenberg, Karl Roland Gao, Jianpeng Oppel, Felix Frank, Stephanie Kang, Na Kindinger, Tim Dieter, Sebastian M. Herbst, Friederike Möhrmann, Lino Dubash, Taronish D. Schulz, Erik R. Strakerjahn, Hendrik Giessler, Klara M. Weber, Sarah Oberlack, Ava Rief, Eva-Maria Strobel, Oliver Bergmann, Frank Lasitschka, Felix Weitz, Jürgen Glimm, Hanno Ball, Claudia R. Cells Article In highly aggressive malignancies like pancreatic cancer (PC), patient-derived tumor models can serve as disease-relevant models to understand disease-related biology as well as to guide clinical decision-making. In this study, we describe a two-step protocol allowing systematic establishment of patient-derived primary cultures from PC patient tumors. Initial xenotransplantation of surgically resected patient tumors (n = 134) into immunodeficient mice allows for efficient in vivo expansion of vital tumor cells and successful tumor expansion in 38% of patient tumors (51/134). Expansion xenografts closely recapitulate the histoarchitecture of their matching patients’ primary tumors. Digestion of xenograft tumors and subsequent in vitro cultivation resulted in the successful generation of semi-adherent PC cultures of pure epithelial cell origin in 43.1% of the cases. The established primary cultures include diverse pathological types of PC: Pancreatic ductal adenocarcinoma (86.3%, 19/22), adenosquamous carcinoma (9.1%, 2/22) and ductal adenocarcinoma with oncocytic IPMN (4.5%, 1/22). We here provide a protocol to establish quality-controlled PC patient-derived primary cell cultures from heterogeneous PC patient tumors. In vitro preclinical models provide the basis for the identification and preclinical assessment of novel therapeutic opportunities targeting pancreatic cancer. MDPI 2019-02-10 /pmc/articles/PMC6406729/ /pubmed/30744205 http://dx.doi.org/10.3390/cells8020142 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ehrenberg, Karl Roland
Gao, Jianpeng
Oppel, Felix
Frank, Stephanie
Kang, Na
Kindinger, Tim
Dieter, Sebastian M.
Herbst, Friederike
Möhrmann, Lino
Dubash, Taronish D.
Schulz, Erik R.
Strakerjahn, Hendrik
Giessler, Klara M.
Weber, Sarah
Oberlack, Ava
Rief, Eva-Maria
Strobel, Oliver
Bergmann, Frank
Lasitschka, Felix
Weitz, Jürgen
Glimm, Hanno
Ball, Claudia R.
Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer
title Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer
title_full Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer
title_fullStr Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer
title_full_unstemmed Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer
title_short Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer
title_sort systematic generation of patient-derived tumor models in pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406729/
https://www.ncbi.nlm.nih.gov/pubmed/30744205
http://dx.doi.org/10.3390/cells8020142
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