Effect of FOS and JUN expression in inmortalized human mesenchymal progenitor cells. Homo sapiens

Mesenchymal progenitor cells (MPCs) have been proposed as cells of origin for sarcomas, while c-Fos and c-Jun transcription factors have been proposed has a oncogenes in sarcoma tumors. Here we study the effects of the induction of c-fos or c-Jun expression in immortalized hMPCs. C-Fos expression in these cells not only generated modifications in cell cycle, but also morphological changes, reduced mobility capacity and impaired adipogenic and osteogenic differentiation potentials. Even more interesting, c-Fos expressing immortalized hMPCs generated tumors with chondrogenic phenotype when implanted in immunodeficient mice. In accordance with these results, c-Fos is expressed at protein level in many human bone tumors, specifically in chondrosarcomas (76% c-fos positive samples) and osteosarcomas (49% c-fos positive samples). c-Jun expression in immortalized hMPCs induces increased proliferation and cell transformation and, once implanted in immunodeficient mice, these cells generate fibroblastic osteosarcomas. Doble c-jun and c-fos expression in immortalized hMPCs also induces cell transformation and yields high grade pleomorphic osteosarcoma tumors when implanted in immunodeficient mice. Overall design: c-DNA was cloned into pOTB7 plasmid, which carries Tomato gene as reporter fluorescent protein. Lentiviral particles were produced by transient calcium phosphate transfection of HEK-293 cells. hMPCs were transduced with those lentiviral particles. Tomato expression was assessed by flow cytometry and c-fos expression was confirmed via qPCR, western blot and immunofluorescence. Cells transduced with lentivirus coding only for fluorescent protein were used as controls. Three independent replicas are provided from each treatment: 3H 1, 3H 2, 3H 3 correspond to hMPCs transduced with control lentiviral particles. 3HF 1, 3HF 2 and 3HF 3 correspond to hMPCs tranduced with lentiviral particles designed for c-fos expression. 3HJ 1, 3HJ 2 and 3HJ 3 correspond to hMPCs tranduced with lentiviral particles designed for c-jun expression. 3HJF 1, 3HJF 2 and 3HJF 3 correspond to hMPCs tranduced with lentiviral particles designed for c-jun and c-fos expression.