Human Chondrosarcoma Cells Acquire an Epithelial-Like GeneExpression Pattern via an Epigenetic Switch: Evidence forMesenchymal-Epithelial Transition during Sarcomagenesis

Abstract EN

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.