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Cells 2019, 8(2), 142; https://doi.org/10.3390/cells8020142

Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer

1
Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
2
Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, 69120 Heidelberg, Germany
3
German Consortium for Translational Cancer Research (DKTK) Heidelberg, 69120 Heidelberg, Germany
4
Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), 01309 Dresden, Germany
5
Center for Personalized Oncology, University Hospital Carl Gustav Carus Dresden at TU Dresden, 01307 Dresden, Germany
6
Department of General Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany
7
Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany
8
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Dresden at TU Dresden, 01307 Dresden, Germany
9
German Consortium for Translational Cancer Research (DKTK) Dresden, 01307 Dresden, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 14 December 2018 / Revised: 30 January 2019 / Accepted: 7 February 2019 / Published: 10 February 2019
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Abstract

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. View Full-Text
Keywords: pancreatic cancer; preclinical in vitro model; patient-derived primary culture pancreatic cancer; preclinical in vitro model; patient-derived primary culture
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Ehrenberg, K.R.; Gao, J.; Oppel, F.; Frank, S.; Kang, N.; Kindinger, T.; Dieter, S.M.; Herbst, F.; Möhrmann, L.; Dubash, T.D.; Schulz, E.R.; Strakerjahn, H.; Giessler, K.M.; Weber, S.; Oberlack, A.; Rief, E.-M.; Strobel, O.; Bergmann, F.; Lasitschka, F.; Weitz, J.; Glimm, H.; Ball, C.R. Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer. Cells 2019, 8, 142.

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