A novel orthotopic animal model of human chondrosarcoma

Summary

Chondrosarcoma is the second most common primary malignant bone tumour in humans. Currently, surgical resection is the only appropriate curative approach as it is relatively unresponsive to traditional chemoand radiotherapy. However, a complete resection is often hindered due to the proximity to organs resulting in a poor outcome of this challenging malignancy. Few novel antitumour agents have been tested on different chondrosarcoma cell lines in vitro so far. In order to qualify new agents in vivo, animal models are often used in which cell lines are subcutaneously injected prior to chemotherapeutical treatment. These types of models often lack relevance to the human chondrosarcoma as the number of agents that fail in the clinic far outweighs those considered effective on in vivo studies. Orthotopic xenograft models however are of much more predictive value. Thus, the development of a novel orthotopic animal model for human chondrosarcoma using a three-dimensional matrix carrying tumour cells, was the aim of this study. For that purpose, SW-1353, a human bone chondrosarcoma cell line, was first cultured in MatrigelTM, followed by orthotopic implantation into10 SCID mice by intra-tibial injection. After 40 days, the animals developed localized bone tumours verified by radiographic and histological examinations. Radiologic and histological sections showed osteolysis and invasive tumour growth. This study demonstrates a promising new method for effective and reproducible orthotopic implantation of human chondrosarcoma. The presented animal model allows further examination and can be used as a predictive preclinical model for anticancer drug activity in humans.

Zusammenfassung

Das Chondrosarkom ist der zweithäufigste primäre bösartige Knochentumor beim Menschen. Derzeit ist die chirurgische Resektion der einzige geeignete kurative Ansatz, da konventionelle herkömmlichen Chemo und Strahlentherapiekonzepte wenig erfolgreich sind. Allerdings ist eine onkologisch notwendige weite Resektion des Tumors oftmals nicht möglich, wegen der räumlichen Nähe zu lebenswichtigen Strukturen. Dies führt dann zu einer schlechten Prognose dieser an spruchs vollen Neoplasie. Einige moderne antineoplastische Substanzen sind bisher auf verschiedenen Chondrosarkom-Zelllinien in vitro getestet worden. Um neue Therapieansätze in vivo zuüberprüfen, werden Tiermodelle verwendet, bei denen vor der chemotherapeutischen Behandlung häufig Zell linien subkutan injiziert werden. Diesen Tiermodellen mangelt es oft an klinischer Relevanz für die Situation des humanen Chondrosarkoms. Das zeigt sich in der hohen Versagensrate von Substanzen in der Klinik, die in In-vivo-Modellen erfolgreich erschienen. Orthotope Xenograft-Modelle haben jedoch viel mehr Aussagekraft. Somit war das Ziel der Untersuchungen die Entwicklung eines neuartigen orthotopen Tiermodells für das Chondrosarkom, unter Verwendung einer dreidimensionalen Matrix als Träger für die Tumorzellen. Zu diesem Zweck wurde SW-1353, eine humane Chondrosarkom-Zelllinie, zuerst in Matrigel® kultiviert und dann in zehn SCID-Mäuse durch eine intratibiale Injektion orthotop implantiert. Nach 40 Tagen entwickelten die Tiere lokale Knochentumoren, die durch radiologische und histologische Untersuchungen verifiziert werden konnten. Konventionelle Röntgenbilder und histologische Schnitte zeigten Osteolysen und invasives Tumorwachstum. Diese Studie zeigt eine viel versprechende neue Methode für eine effektive und reproduzierbare orthotope Implantation von humanen Chondrosarkomzellen. Das vorgestellte Tiermodell erlaubt weitere Untersuchungen und kann als prädiktives präklinisches Modell zurÜberprüfung der Effektivität neuartiger Therapieansätze beim Chondrosarkom eingesetzt werden.

Keywords

Chondrosarcoma - orthotopic - xenograft - primary malignant bone tumour - animal model

Schlüsselwörter

Chondrosarkom - orthotopisch - Xenograft - primärer maligner Knochentumor - Tiermodell

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