Role of Activator Protein-1 Complex on the Phenotype of Human Osteosarcomas Generated from Mesenchymal Stem Cells. (11th August 2018)

• Record Type: Journal Article
• Authors: Gambera, Stefano; Abarrategi, Ander; Rodríguez-Milla, Miguel A.; Mulero, Francisca; Menéndez, Sofía T.; Rodriguez, René; Navarro, Samuel; García-Castro, Javier
• Is Part Of: Stem cells. Volume 36:Number 10(2018)
• Page Start: 1487
• Page End: 1500
• Publication Date: 2018-08-11
• Subjects: Mesenchymal stem cells -- Osteosarcoma -- p53 -- Rbc-JUN -- c-FOS; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2869
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : Osteosarcoma (OS) is a highly aggressive bone tumor that usually arises intramedullary at the extremities of long bones. Due to the fact that the peak of incidence is in the growth spurt of adolescence, the specific anatomical location, and the heterogeneity of cells, it is believed that osteosarcomagenesis is a process associated with bone development. Different studies in murine models showed that the tumor-initiating cell in OS could be an uncommitted mesenchymal stem cell (MSC) developing in a specific bone microenvironment. However, only a few studies have reported transgene-induced human MSCs transformation and mostly obtained undifferentiated sarcomas. In our study, we demonstrate that activator protein 1 family members induce osteosarcomagenesis in immortalized hMSC. c-JUN or c-JUN/c-FOS overexpression act as tumorigenic factors generating OS with fibroblastic or pleomorphic osteoblastic phenotypes, respectively. Abstract : Activator protein 1 family members induce tumoral transformation of immortalized human Mesenchymal Stem Cells (hMSC). c-JUN or c-JUN/c-FOS overexpression, using lentiviral vectors (Lenti c-Jun and Lenti c-Fos), act as tumorigenic factors generating osteosarcomas with fibroblastic or pleomorphic osteoblastic phenotypes, respectively.