Journal
JOURNAL OF ORTHOPAEDIC RESEARCH
Volume 29, Issue 6, Pages 938-946Publisher
WILEY
DOI: 10.1002/jor.21304
Keywords
osteosarcoma; metastasis; mouse model; lacZ; lung perfusion; syngeneic; single cell tracking
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Funding
- Krebsliga of the Kanton Zurich
- Walter L. and Johanna Wolf Foundation, Zurich
- Lydia Hochstrasser Foundation, Zurich
- Swiss National Science Foundation, SNF, Switzerland
- Schweizerischer Verein Balgrist
- University of Zurich
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More effective treatment of patients with metastasizing osteosarcoma (OS) with a mean 5-year survival rate of <20% requires more detailed knowledge on the complex mechanisms of metastasis for the design of new drugs, which selectively target metastasizing cells. Moreover, novel diagnostic imaging technology for early detection of metastases is needed. Mouse models, which reproduce human metastasizing OS and allow visualization of single metastatic cells are instrumental for preclinical testing of new pharmaceuticals and diagnostic instruments. Here, the low metastatic Dunn cell line and its highly metastatic LM8 subline, both equipped with a constitutively expressed lacZ gene, were used to improve the well-established OS models in syngeneic C3H mice to achieve ex vivo visualization of single metastatic cells in affected organs by X-gal staining. These models, combined with a technique for in situ high quality lung tissue-maintaining perfusion revealed, as a novel finding, single metastasizing Dunn cells in lung and liver. Importantly, constitutive lacZ gene expression did not affect in vitro and in vivo tumorigenic and metastatic properties of Dunn and LM8 cells. Thus, these improved Dunn and LM8 OS mouse models will in the future serve as a benchmark for the development of new metastasis-targeting drugs and metastasis-imaging technology. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:938-946, 2011
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