title: Human Chondrosarcoma Cells Acquire an Epithelial-Like Gene Expression Pattern via an Epigenetic Switch: Evidence for Mesenchymal-Epithelial Transition during Sarcomagenesis.
abstract: 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.
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Fitzgerald
authors.forename: Francoise
authors.initials: F
authors.lastname: Gourronc
authors.forename: Melissa L T
authors.initials: ML
authors.lastname: Teoh
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Provenzano
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Case
authors.forename: James A
authors.initials: JA
authors.lastname: Martin
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Domann