A novel orthotopic murine model provides insights into cellular and molecular characteristics contributing to human osteosarcoma

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Abstract
As a reliable model for osteosarcoma is lacking, three human cell lines (SaOS-2, U2OS and 143B) were evaluated in cell-based assays for proliferation, adhesion, migration, invasion, anchorage-independent growth, angiogenesis, mineralised nodule formation, plasmid transfection and oligonucleotide transfection. Tumor take and metastasis after orthotopic injection of the three cell lines into mice was monitored. The levels of expression of typical bone markers were determined with semi-quantitative RT-PCR in cultured cells, primary tumors, and for the SaOS-2 cell line, the metastases. Tumors grew and spread to the lungs within 3 and 5 weeks respectively, mimicking the clinical progression of the disease as analysed by x-ray. Expression of molecular markers in SaOS-2 indicated a mostly differentiated cell type at the primary and secondary sites. The ability of osteosarcoma cells to interact with collagen-1 and to form mineralised deposits correlated positively with tumor aggression in vivo. Expression of alkaline phosphatase was a common theme in both tumor models at the primary site. The newly established SaOS-2 model should allow the testing of candidate anti-osteosarcoma agents as well as dissection of more intricate mechanisms involved in human osteosarcoma.