Human chondrosarcoma cells acquire an epithelial-like gene expression pattern via an epigenetic switch: Evidence for mesenchymal-epithelial transition during sarcomagenesis

Frederick E. Domann, Matthew P. Fitzgerald, Francoise Gourronc, Melissa L.T. Teoh, Matthew J. Provenzano, Adam J. Case, James A. Martin

Research output: Contribution to journalReview article

27 Scopus citations

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 14-3-3 , all of which are governed epigenetically through cytosine methylation. Indeed, loss of cytosine methylation was tightly associated with acquired expression of both maspin and 14-3-3 in chondrosarcomas. In contrast, chondrocyte cells were negative for maspin and 14-3-3 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.

Original languageEnglish (US)
Article number598218
JournalSarcoma
Volume2011
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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