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LacZ transgene expression in the subcutaneous Dunn/LM8 osteosarcoma mouse model allows for the identification of micrometastasis


Arlt, M J E; Banke, I J; Walters, D K; Puskas, G J; Steinmann, P; Muff, R; Born, W; Fuchs, B (2011). LacZ transgene expression in the subcutaneous Dunn/LM8 osteosarcoma mouse model allows for the identification of micrometastasis. Journal of Orthopaedic Research, 29(6):938-946.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Balgrist University Hospital, Swiss Spinal Cord Injury Center
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2011
Deposited On:27 Dec 2011 16:06
Last Modified:05 Apr 2016 15:16
Publisher:Wiley-Blackwell
ISSN:0736-0266
Funders: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
Publisher DOI:https://doi.org/10.1002/jor.21304
PubMed ID:21284029

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