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Open Access Research article

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

Maurice Balke12*, Anna Neumann3, Károly Szuhai45, Konstantin Agelopoulos6, Christian August7, Georg Gosheger2, Pancras CW Hogendoorn4, Nick Athanasou8, Horst Buerger9 and Martin Hagedorn1011

Author Affiliations

1 Department of Trauma and Orthopedic Surgery, University of Witten-Herdecke, Cologne-Merheim Medical Center, Ostmerheimer Str., 200, 51109 Cologne, Germany

2 Department of Orthopedic Surgery, University of Muenster, Albert-Schweitzer-Str. 33, 48149 Muenster, Germany

3 Gerhard-Domagk-Institute of Pathology, University of Muenster, Domagkstr. 17, 48149 Muenster, Germany

4 Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands

5 Department of Molecular Cell Biology, Leiden University Medical Center, Einthovenweg 20, 2300 RC, Leiden, The Netherlands

6 Department of Medicine, Hematology and Oncology, University of Muenster Domagkstrasse 3, 48149 Muenster, Germany

7 Institute of Pathology, Klinikum Hanau GmbH, Leimenstr. 20, 63450 Hanau am Main, Germany

8 Department of Pathology, Nuffield Orthopaedic Centre, University of Oxford, Oxford OX3 7LD, UK

9 Institute of Pathology, Husener Str. 46 a 33098 Paderborn, Germany

10 INSERM U1029, Avenue des Facultés, Bâtiment B2, 33405 Talence cedex, France

11 University Bordeaux 1, Avenue des Facultés, Bâtiment B2, 33405 Talence cedex, France

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BMC Cancer 2011, 11:241  doi:10.1186/1471-2407-11-241

Published: 13 June 2011

Abstract

Background

Because 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.

Methods

Fresh 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).

Results

The 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.

Conclusions

A 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.