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Chondrocytes are mesenchymally derived cells that reportedly acquire some epithelial characteristics; however, whether this is a progression through a mesenchymal to epithelial transition (MET) during chondrosarcoma development is still a matter of investigation. We observed that chondrosarcoma cells acquired the expression of four epithelial markers,  E-cadherin,desmocollin 3, maspin , and  14-3-3σ , all of which are governed epigenetically through cytosine methylation. Indeed, loss of cytosine methylation was tightly associated with acquired expression of both  maspin  and  14-3-3σ  in chondrosarcomas. In contrast, chondrocyte cells were negative for  maspin  and  14-3-3σ  and displayed nearly complete DNA methylation. Robust activation of these genes was also observed in chondrocyte cells following 5-aza-dC treatment. We also examined the transcription factor  snail  which has been reported to be an important mediator of epithelial to mesenchymal transitions (EMTs). In chondrosarcoma cells  snail  is downregulated suggesting a role for loss of  snail  expression in lineage maintenance. Taken together, these results document an epigenetic switch associated with an MET-like phenomenon that accompanies chondrosarcoma progression.

sarcoma

Human Chondrosarcoma Cells Acquire an Epithelial-Like Gene Expression Pattern via an Epigenetic Switch: Evidence for Mesenchymal-Epithelial Transition during Sarcomagenesis