c-Fos induces chondrogenic tumor formation in immortalized human mesenchymal progenitor cells
| Autor: | Francisca Mulero, Probir Chakravarty, Alexander Waclawiczek, Raquel Pérez-Tavarez, Miguel Ángel Rodríguez-Milla, Ander Abarrategi, Stefano Gambera, Kevin Rouault-Pierre, Javier García-Castro, Arantzazu Alfranca, Cesar Trigueros, Samuel Navarro, Dominique Bonnet |
|---|---|
| Přispěvatelé: | Instituto de Salud Carlos III, Comunidad de Madrid, Ministerio de Economía y Competitividad (España), European Regional Development Fund |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Carcinogenesis Cell lcsh:Medicine Mice SCID Article Cell Line 03 medical and health sciences Mice 0302 clinical medicine Mice Inbred NOD medicine Animals Humans Progenitor cell lcsh:Science Regulation of gene expression Multidisciplinary Oncogene Chemistry Mesenchymal stem cell lcsh:R Genes fos Mesenchymal Stem Cells Sarcoma Chondrogenesis Phenotype Cell biology Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Cell Transformation Neoplastic Cell culture 030220 oncology & carcinogenesis lcsh:Q Proto-Oncogene Proteins c-fos |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) Repisalud Instituto de Salud Carlos III (ISCIII) |
| Popis: | 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. This work was supported by grants from the Fondo de Investigaciones Sanitarias (FIS: PI11/00377 to J.G.-C.; and RTICC: RD12/0036/0027 to J.G-C, RD12/0036/0020 to S.M.) and the Madrid Regional Government (CellCAM; P2010/BMD-2420 to J.G.-C) in Spain. A.A. was supported by Juan de la Cierva program of the Spanish Plan Nacional (MINECO) and Sara Borrell program of the ISCIII/FEDER. A.Al. was supported by the “Miguel Servet” program of the ISCIII/FEDER. We gratefully acknowledge support from Asociación Pablo Ugarte (CIF G86121019) and AFANION (CIF G02223733). The experiments were approved by the appropriate committees. Sí |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|