A short-term in vivo model for giant cell tumor of bone

BMC Cancer

Research Article

Konstantin Agelopoulos¹  Georg Gosheger²  Pancras CW Hogendoorn³  Károly Szuhai⁴  Nick Athanasou⁵  Maurice Balke⁶  Anna Neumann⁷  Martin Hagedorn⁸  Horst Buerger⁹  Christian August^1,10 

[1] Department of Medicine, Hematology and Oncology, University of Muenster Domagkstrasse 3, 48149, Muenster, Germany;Department of Orthopedic Surgery, University of Muenster, Albert-Schweitzer-Str. 33, 48149, Muenster, Germany;Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2300, Leiden, RC, The Netherlands;Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2300, Leiden, RC, The Netherlands;Department of Molecular Cell Biology, Leiden University Medical Center, Einthovenweg 20, 2300, Leiden, RC, The Netherlands;Department of Pathology, Nuffield Orthopaedic Centre, University of Oxford, OX3 7LD, Oxford, UK;Department of Trauma and Orthopedic Surgery, University of Witten-Herdecke, Cologne-Merheim Medical Center, Ostmerheimer Str., 200, 51109, Cologne, Germany;Department of Orthopedic Surgery, University of Muenster, Albert-Schweitzer-Str. 33, 48149, Muenster, Germany;Gerhard-Domagk-Institute of Pathology, University of Muenster, Domagkstr. 17, 48149, Muenster, Germany;INSERM U1029, Avenue des Facultés, Bâtiment B2, 33405, Talence cedex, France;University Bordeaux 1, Avenue des Facultés, Bâtiment B2, 33405, Talence cedex, France;Institute of Pathology, Husener Str. 46 a 33098 Paderborn, Germany;Institute of Pathology, Klinikum Hanau GmbH, Leimenstr. 20, 63450, Hanau am Main, Germany;

关键词: Giant Cell;    Denosumab;    Giant Cell Tumor;    Giant Cell Tumor;    Human Osteosarcoma Cell Line;   

DOI  :  10.1186/1471-2407-11-241

 received in 2010-12-16, accepted in 2011-06-13,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundBecause of the lack of suitable in vivo models of giant cell tumor of bone (GCT), little is known about its underlying fundamental pro-tumoral events, such as tumor growth, invasion, angiogenesis and metastasis. There is no existing cell line that contains all the cell and tissue tumor components of GCT and thus in vitro testing of anti-tumor agents on GCT is not possible. In this study we have characterized a new method of growing a GCT tumor on a chick chorio-allantoic membrane (CAM) for this purpose.MethodsFresh tumor tissue was obtained from 10 patients and homogenized. The suspension was grafted onto the CAM at day 10 of development. The growth process was monitored by daily observation and photo documentation using in vivo biomicroscopy. After 6 days, samples were fixed and further analyzed using standard histology (hematoxylin and eosin stains), Ki67 staining and fluorescence in situ hybridization (FISH).ResultsThe suspension of all 10 patients formed solid tumors when grafted on the CAM. In vivo microscopy and standard histology revealed a rich vascularization of the tumors. The tumors were composed of the typical components of GCT, including (CD51+/CD68+) multinucleated giant cells whichwere generally less numerous and contained fewer nuclei than in the original tumors. Ki67 staining revealed a very low proliferation rate. The FISH demonstrated that the tumors were composed of human cells interspersed with chick-derived capillaries.ConclusionsA reliable protocol for grafting of human GCT onto the chick chorio-allantoic membrane is established. This is the first in vivo model for giant cell tumors of bone which opens new perspectives to study this disease and to test new therapeutical agents.

【 授权许可】

CC BY   
© Balke et al; licensee BioMed Central Ltd. 2011