Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer

• Published in: Cells (Basel, Switzerland) Vol. 8; no. 2; p. 142
• Main Authors: Ehrenberg, Karl Roland, Gao, Jianpeng, Oppel, Felix, Frank, Stephanie, Kang, Na, 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.02.2019; MDPI
• Subjects: Adenocarcinoma; Adenosquamous; Animals; Cell culture; Cell Line, Tumor; Cell Proliferation; Cloning; Decision making; Epithelial cells; Experiments; Female; Flow cytometry; Humans; Immunodeficiency; Laboratory animals; Male; Mice; Models, Biological; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - pathology; patient-derived primary culture; Patients; preclinical in vitro model; Squamous cell carcinoma; Surgery; Tumor cells; Tumors; Xenograft Model Antitumor Assays; Xenografts; England; United Kingdom > UK; United States > US; Germany; preclinical in vitro model; pancreatic cancer; patient-derived primary culture
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8020142

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.