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Establishment of a patient-derived orthotopic osteosarcoma mouse model

Blattmann, Claudia ; Thiemann, Markus ; Stenzinger, Albrecht ; Roth, Eva K. ; Dittmar, Anne ; Witt, Hendrik ; Lehner, Burkhard ; Renker, Eva ; Jugold, Manfred ; Eichwald, Viktoria ; Weichert, Wilko ; Huber, Peter E. ; Kulozik, Andreas E.

In: Journal of Translational Medicine, 13 (2015), Nr. 136. pp. 1-10. ISSN 1479-5876

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Download (4MB) | Lizenz: Creative Commons LizenzvertragEstablishment of a patient-derived orthotopic osteosarcoma mouse model by Blattmann, Claudia ; Thiemann, Markus ; Stenzinger, Albrecht ; Roth, Eva K. ; Dittmar, Anne ; Witt, Hendrik ; Lehner, Burkhard ; Renker, Eva ; Jugold, Manfred ; Eichwald, Viktoria ; Weichert, Wilko ; Huber, Peter E. ; Kulozik, Andreas E. underlies the terms of Creative Commons Attribution 3.0 Germany

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Abstract

Background: Osteosarcoma (OS) is the most common pediatric primary malignant bone tumor. As the prognosis for patients following standard treatment did not improve for almost three decades, functional preclinical models that closely reflect important clinical cancer characteristics are urgently needed to develop and evaluate new treatment strategies. The objective of this study was to establish an orthotopic xenotransplanted mouse model using patient-derived tumor tissue. Methods: Fresh tumor tissue from an adolescent female patient with osteosarcoma after relapse was surgically xenografted into the right tibia of 6 immunodeficient BALB/c Nu/Nu mice as well as cultured into medium. Tumor growth was serially assessed by palpation and with magnetic resonance imaging (MRI). In parallel, a primary cell line of the same tumor was established. Histology and high-resolution array-based comparative genomic hybridization (aCGH) were used to investigate both phenotypic and genotypic characteristics of different passages of human xenografts and the cell line compared to the tissue of origin. Results: A primary OS cell line and a primary patient-derived orthotopic xenotranplanted mouse model were established. MRI analyses and histopathology demonstrated an identical architecture in the primary tumor and in the xenografts. Array-CGH analyses of the cell line and all xenografts showed highly comparable patterns of genomic progression. So far, three further primary patient-derived orthotopic xenotranplanted mouse models could be established. Conclusion: We report the first orthotopic OS mouse model generated by transplantation of tumor fragments directly harvested from the patient. This model represents the morphologic and genomic identity of the primary tumor and provides a preclinical platform to evaluate new treatment strategies in OS.

Item Type: Article
Journal or Publication Title: Journal of Translational Medicine
Volume: 13
Number: 136
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 14 Jan 2016 10:11
Date: 2015
ISSN: 1479-5876
Page Range: pp. 1-10
Faculties / Institutes: Medizinische Fakultät Heidelberg > Orthopädische Klinik
Service facilities > German Cancer Research Center (DKFZ)
Medizinische Fakultät Heidelberg > Universitätskinderklinik
Medizinische Fakultät Heidelberg > Radiologische Universitätsklinik
Medizinische Fakultät Heidelberg > Pathologisches Institut
Subjects: 610 Medical sciences Medicine
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