Despite Osteosarcoma (OS) being the most common primary malignant bone tumor in children and young adults, little clarity exists in where the cell of origin exists in the pathway of differentiation between a human mesenchymal stem cell (hMSC) and a mature osteoblast. It is similarly unclear the primary genetic alterations which initiate oteosarcoma formation in patients. Since high grade OS usually demonstrates histologic variability, and the potential for multilineage differentiation, along with some direct experimental observations some consider hMSC as the cell of origin of OS whereas others believe the pre-osteoblast or osteoblast to be the mot likely cell of origin. Our previous studies have shown that serially introducing 3 different viral constructs, hTERT, SV40TAg, and H-RAS, transforms hMSC into 2 distinct sarcomas cell lines, but not OS. This may be attributable to the fact that oncogenic H-Ras does not seem to play a direct role in the pathogenesis of OS. Therefore, the MSC-TS cell line, hMSC transfected with hTERT and SV40TAg can be used as a platform for further analysis of the impact of genetic transformation of hMSCs. The MSC-TS cells were transformed with lentivirus containing human β-catenin (β), and IGF-1R (I) , separately. Both β-catenin and IGF-1R have been suggested to be involved in the pathogenesis of OS due to their proliferative and/or anti-apoptotic effects. Drug resistant colonies were picked up 21 days after selection to obtain stably transfected cell lines, MSC-TS-β, and MSC-TS-I, respectively. Western blots were carried out to detect the protein of β-catenin and IGF-1R, respectively. Clones, which have highest, lowest, and intermediate protein levels were selected, and comparison between the lines and characterizations are completed and underway. Further characterization includes: 1) Soft Agar Assays , 2)Subcutaneous/Orthotopic Tumorigenicity Assays,3) Routine histological examination and also staining with immunohistochemical markers, 4) Microarray Analysis, 5) Spectral Karyotyping / Comparative Genomic Hybridization, 6) Motility and Migration Assays, and 7) Differentiation Assays. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 418.
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