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oai:repisalud.isciii.es:20.500.12105/155502025-05-07T10:36:07Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19616col_20.500.12105_16990

00925njm 22002777a 4500 dc Gambera, Stefano author Abarrategi, Ander author Rodriguez-Milla, Miguel A author Mulero, Francisca author Menéndez, Sofía T author Rodriguez, Rene author Navarro, Samuel author Garcia-Castro, Javier author 2018-10 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. Stem Cells 2018;36:1487-1500. Stem Cells. 2018 Oct;36(10):1487-1500. 10.1002/stem.2869 1549-4918 Stem cells (Dayton, Ohio) 30001480 http://hdl.handle.net/20.500.12105/15550 Mesenchymal stem cells Osteosarcoma p53 Rbc-JUN c-FOS Role of Activator Protein-1 Complex on the Phenotype of Human Osteosarcomas Generated from Mesenchymal Stem Cells