Unidad de Biotecnología Celular, Instituto de Salud Carlos III, Madrid, E-28021, Spain.
Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, London, WC2A 3LY, UK.
Sci Rep. 2018 Oct 23;8(1):15615. doi: 10.1038/s41598-018-33689-0.
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.
间充质祖细胞 (MPCs) 被假设为肉瘤的起源细胞，c-Fos 转录因子已被证明在骨肿瘤中作为癌基因发挥作用。在这项研究中，我们表明 c-Fos 存在于大多数具有软骨表型的肉瘤中，而其他多个基因与 c-Fos 的表达模式有关。为了进一步确定 c-Fos 在肉瘤发生中的作用，我们在原代人 MPCs (hMPCs)、永生化 hMPCs 和转化的鼠 MPCs (mMPCs) 中表达了它。在永生化的 hMPCs 中，c-Fos 的表达导致形态发生变化，降低了迁移能力，并损害了成脂和成骨分化潜能。值得注意的是，表达 c-Fos 的永生化 hMPCs 或 mMPCs 产生了具有软骨表型和形态的肿瘤。因此，我们在这里表明 c-Fos 蛋白在肉瘤中具有关键作用，并且在永生化 MPCs 中表达 c-Fos 会导致细胞转化和软骨瘤形成。
