A mouse model of pulmonary metastasis from spontaneous osteosarcoma monitored in vivo by Luciferase imaging.
BACKGROUND
Osteosarcoma (OSA) is lethal when metastatic after chemotherapy and/or surgical treatment. Thus animal models are necessary to study the OSA metastatic spread and to validate novel therapies able to control the systemic disease. We report the development of a syngeneic (Balb/c) murine OSA model, using a cell line derived from a spontaneous murine tumor.


METHODS
The tumorigenic and metastatic ability of OSA cell lines were assayed after orthotopic injection in mice distal femur. Expression profiling was carried out to characterize the parental and metastatic cell lines. Cells from metastases were propagated and engineered to express Luciferase, in order to follow metastases in vivo.


RESULTS
Luciferase bioluminescence allowed to monitor the primary tumor growth and revealed the appearance of spontaneous pulmonary metastases. In vivo assays showed that metastasis is a stable property of metastatic OSA cell lines after both propagation in culture and luciferase trasduction. When compared to parental cell line, both unmodified and genetically marked metastatic cells, showed comparable and stable differential expression of the enpp4, pfn2 and prkcd genes, already associated to the metastatic phenotype in human cancer.


CONCLUSIONS
This OSA animal model faithfully recapitulates some of the most important features of the human malignancy, such as lung metastatization. Moreover, the non-invasive imaging allows monitoring the tumor progression in living mice. A great asset of this model is the metastatic phenotype, which is a stable property, not modifiable after genetic manipulation.
Miretti
Silvia
S
Department of Morphophysiology, School of Veterinary Medicine, University of Torino, Grugliasco, Turin, Italy. silvia.miretti@unito.it
Roato
Ilaria
I
Taulli
Riccardo
R
Ponzetto
Carola
C
Cilli
Michele
M
Olivero
Martina
M
Di Renzo
Maria Flavia
MF
Godio
Laura
L
Albini
Adriana
A
Buracco
Paolo
P
Ferracini
Riccardo
R
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D008156:Luciferases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D012516:Osteosarcoma / Q000473:pathology*
D008156:Luciferases