Establishment of the First Well-differentiated Human Pancreatic Neuroendocrine Tumor Model.

Autor:	Benten D; I. Medical Department - Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of Gastroenterology, Helios Klinik Duisburg, Duisburg, Germany., Behrang Y; I. Medical Department - Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Unrau L; Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Weissmann V; Department of General-, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Wolters-Eisfeld G; Department of General-, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Burdak-Rothkamm S; Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Stahl FR; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Anlauf M; Institute of Pathology, Limburg, Germany., Grabowski P; Department of Gastroenterology, Rheumatology and Infectious Diseases, Charite Campus Benjamin Franklin, Berlin, Germany., Möbs M; Institute of Pathology, Charité - Universitaetsmedizin Berlin, Berlin, Germany., Dieckhoff J; Department for Interventional and Diagnostic Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Sipos B; Department of Pathology, University Hospital Tübingen, Tübingen, Germany., Fahl M; I. Medical Department - Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Eggers C; I. Medical Department - Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Perez D; Department of General-, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Bockhorn M; Department of General-, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Izbicki JR; Department of General-, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Lohse AW; I. Medical Department - Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Schrader J; I. Medical Department - Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. j.schrader@uke.de.; Department of General-, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jazyk:	angličtina
Zdroj:	Molecular cancer research : MCR [Mol Cancer Res] 2018 Mar; Vol. 16 (3), pp. 496-507. Date of Electronic Publication: 2018 Jan 12.
DOI:	10.1158/1541-7786.MCR-17-0163
Abstrakt:	Clinical options for systemic therapy of neuroendocrine tumors (NET) are limited. Development of new drugs requires suitable representative in vitro and in vivo model systems. So far, the unavailability of a human model with a well-differentiated phenotype and typical growth characteristics has impaired preclinical research in NET. Herein, we establish and characterize a lymph node-derived cell line (NT-3) from a male patient with well-differentiated pancreatic NET. Neuroendocrine differentiation and tumor biology was compared with existing NET cell lines BON and QGP-1. In vivo growth was assessed in a xenograft mouse model. The neuroendocrine identity of NT-3 was verified by expression of multiple NET-specific markers, which were highly expressed in NT-3 compared with BON and QGP-1. In addition, NT-3 expressed and secreted insulin. Until now, this well-differentiated phenotype is stable since 58 passages. The proliferative labeling index, measured by Ki-67, of 14.6% ± 1.0% in NT-3 is akin to the original tumor (15%-20%), and was lower than in BON (80.6% ± 3.3%) and QGP-1 (82.6% ± 1.0%). NT-3 highly expressed somatostatin receptors (SSTRs: 1, 2, 3, and 5). Upon subcutaneous transplantation of NT-3 cells, recipient mice developed tumors with an efficient tumor take rate (94%) and growth rate (139% ± 13%) by 4 weeks. Importantly, morphology and neuroendocrine marker expression of xenograft tumors resembled the original human tumor. Implications: High expression of somatostatin receptors and a well-differentiated phenotype as well as a slow growth rate qualify the new cell line as a relevant model to study neuroendocrine tumor biology and to develop new tumor treatments. Mol Cancer Res; 16(3); 496-507. ©2018 AACR . (©2018 American Association for Cancer Research.)
Databáze:	MEDLINE
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