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Sarcoma
Volume 2012 (2012), Article ID 164803, 10 pages
http://dx.doi.org/10.1155/2012/164803
Research Article

β-Catenin Does Not Confer Tumorigenicity When Introduced into Partially Transformed Human Mesenchymal Stem Cells

1The Department of Pediatrics, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA
2The Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA
3The Department of Orthopaedic Surgery, Montefiore Medical Center, Bronx, NY 10467, USA
4Division Hematology/Oncology, Department of Pediatrics, The Children’s Hospital at Montefiore, Room 300, Rosenthal Building, 3415 Bainbridge Avenue, Bronx, NY 10467, USA
5Oncology Section, The Department of Orthopedics Surgery, First Affiliated Hospital of PLA General Hospital, Beijing 100037, China
6The Department of Orthopedics Surgery, College of Medicine, Kosin University Gospel Hospital, Busan 602-702, Republic of Korea
7Department of Pediatrics and Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA
8Division of Hematology/Oncology, Department of Pediatrics, The Children's Hospital at Montefiore, Room 300, Rosenthal Building, 3415 Bainbridge Avenue, Bronx, NY 10467, USA

Received 5 July 2012; Revised 23 September 2012; Accepted 23 September 2012

Academic Editor: H. Gelderblom

Copyright © 2012 Sajida Piperdi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Although osteosarcoma is the most common primary malignant bone tumor in children and adolescents, its cell of origin and the genetic alterations are unclear. Previous studies have shown that serially introducing hTERT, SV40 large TAg, and H-Ras transforms human mesenchymal stem cells into two distinct sarcomas cell populations, but they do not form osteoid. In this study, β-catenin was introduced into mesenchymal stem cells already containing hTERT and SV40 large TAg to analyze if this resulted in a model which more closely recapitulated osteosarcoma. Results. Regardless of the level of induced β-catenin expression in the stable transfectants, there were no marked differences induced in their phenotype or invasion and migration capacity. Perhaps more importantly, none of them formed tumors when injected into immunocompromised mice. Moreover, the resulting transformed cells could be induced to osteogenic and chondrogenic differentiation but not to adipogenic differentiation. Conclusions. β-catenin, although fostering osteogenic differentiation, does not induce the malignant features and tumorigenicity conveyed by oncogenic H-RAS when introduced into partly transformed mesenchymal stem cells. This may have implications for the role of β-catenin in osteosarcoma pathogenesis. It also may suggest that adipogenesis is an earlier branch point than osteogenesis and chondrogenesis in normal mesenchymal differentiation.