An orthotopic, postsurgical model of luciferase transfected murine osteosarcoma with spontaneous metastasis.
Osteosarcoma (OS) is the most common bone tumor in humans. Newer, more clinically relevant models of OS are required to investigate novel therapeutics. The ability to study spontaneous micrometastases in the absence of a primary tumor is important since this is the manner in which most patients are treated clinically. Therefore, we have developed a novel model of murine OS using the DLM8 cell line, which is syngeneic to C3H mice. We have engineered these cells to express firefly luciferase so the development of metastases can be followed serially and non-invasively. These cells form osteolytic/osteoproductive lesions and metastasize spontaneously after orthotopic implantation in the proximal tibia, and the development of soft-tissue metastasis can be followed serially by luciferase expression following amputation. We have demonstrated a significant prolongation of disease-free and overall survival in the surgical adjuvant setting following treatment with doxorubicin or carboplatin, drugs which form the mainstay of treatment for human OS. In conclusion, we have developed a novel surgical adjuvant model of metastatic OS in immunocompetent mice that closely recapitulates the clinical situation, allowing the evaluation of novel therapeutics in the context of minimal residual disease.
Sottnik
Joseph L
JL
Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA. jsottnik@rams.colostate.edu
Duval
Dawn L
DL
Ehrhart
E J
EJ
Thamm
Douglas H
DH
D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*; D016190:Carboplatin / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology*; D009368:Neoplasm Transplantation / Q000379:methods; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*; D016019:Survival Analysis; D013977:Tibia / Q000473:pathology / Q000601:surgery; D014162:Transfection / Q000379:methods
D004317:Doxorubicin; D016190:Carboplatin; D008156:Luciferases