title: An orthotopic mouse model of small cell lung cancer reflects the clinical course in patients.
abstract: Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with very poor prognosis due to early metastatic spread and development of chemoresistance. In the last 30 years the study of SCLC has been constrained by a lack of primary human tumor specimen thus highlighting the need of a suitable mouse model. In this article we present the establishment of an orthotopic xenograft mouse model which accurately reproduced the clinical course of SCLC. Orthotopic implantation enabled engraftment of primary lung tumors in all injected mice. Furthermore, immunodeficiency of mice allowed formation of spontaneous metastases in characteristic organs. Bioluminescence Imaging, Magnetic Resonance Imaging and Positron emission tomography were applied to monitor engraftment, metabolism and the exact growth of tumors over time. In order to mimic the extensive disease stage, mice were injected with aggressive human chemoresistant cells leading to development of chemoresistant tumors and early metastatic spread. As a proof of concept treatment of tumor-bearing mice with conventional chemotherapeutics reduced tumor volumes, but a complete regression of tumors was not achieved. By mimicking the extensive disease stage our mouse model can facilitate the study of mechanisms contributing to chemoresistance and metastasis formation, as well as drug screening and evaluation of new treatment strategies for SCLC patients.
authors.affiliation: Department of Hematology/Oncology and Stem Cell Transplantation, University Medical Center, Hugstetter Str. 55, 70106, Freiburg, Germany.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Taromi
authors.affiliation: Department of Pathology, University Medical Center, Freiburg, Germany.
authors.forename: Gian
authors.initials: G
authors.lastname: Kayser
authors.affiliation: Department of Radiology Medical Physics, University Medical Center, Freiburg, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: von Elverfeldt
authors.affiliation: Department of Radiology Medical Physics, University Medical Center, Freiburg, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Reichardt
authors.affiliation: Institute of Nuclear Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Braun
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA.|Institute of Nuclear Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Weber
authors.affiliation: Department of Hematology/Oncology and Stem Cell Transplantation, University Medical Center, Hugstetter Str. 55, 70106, Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Zeiser
authors.affiliation: Department of Hematology/Oncology and Stem Cell Transplantation, University Medical Center, Hugstetter Str. 55, 70106, Freiburg, Germany. meike.burger@uniklinik-freiburg.de.|Faculty of Medical and Life Sciences, University Futwangen, Campus Schwenningen, Jakob-Kienzle-Str. 17, 78054, Villingen-Schwenningen, Germany. meike.burger@uniklinik-freiburg.de.
authors.forename: Meike
authors.initials: M
authors.lastname: Burger
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D008168:Lung; D008279:Magnetic Resonance Imaging; D051379:Mice; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D055752:Small Cell Lung Carcinoma / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D014183:Transplantation, Heterologous / Q000379:methods; D023041:Xenograft Model Antitumor Assays
keywords: Chemoresistance; Metastasis; Mouse model; Orthotop; Small cell lung cancer