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c-Fos induces chondrogenic tumor formation in immortalized human mesenchymal progenitor cells

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posted on 25.06.2020 by Ander Abarrategi, Stefano Gambera, Arantzazu Alfranca, Miguel A Rodriguez-Milla, Raquel Perez-Tavarez, Kevin Rouault-Pierre, Alexander Waclawiczek, Probir Chakravarty, Francisca Mulero, César Trigueros, Samuel Navarro, Dominique Bonnet, Javier García-Castro
Mesenchymal progenitor cells (MPCs) have been hypothesized as cells of origin for sarcomas, and c-Fos transcription factor has been showed to act as an oncogene in bone tumors. In this study, we show c-Fos is present in most sarcomas with chondral phenotype, while multiple other genes are related to c-Fos expression pattern. To further define the role of c-Fos in sarcomagenesis, we expressed it in primary human MPCs (hMPCs), immortalized hMPCs and transformed murine MPCs (mMPCs). In immortalized hMPCs, c-Fos expression generated morphological changes, reduced mobility capacity and impaired adipogenic- and osteogenic-differentiation potentials. Remarkably, immortalized hMPCs or mMPCs expressing c-Fos generated tumors harboring a chondrogenic phenotype and morphology. Thus, here we show that c-Fos protein has a key role in sarcomas and that c-Fos expression in immortalized MPCs yields cell transformation and chondrogenic tumor formation.

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