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

25 Citations (Scopus)

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 - Apr 28 2011

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Chondrosarcoma
Epithelial-Mesenchymal Transition
Epigenomics
Epithelial Cells
Gene Expression
Chondrocytes
Cytosine
Snails
Cadherins
Methylation
Desmocollins
DNA Methylation
Transcriptional Activation
Down-Regulation
Maintenance
SERPIN-B5

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Human chondrosarcoma cells acquire an epithelial-like gene expression pattern via an epigenetic switch : Evidence for mesenchymal-epithelial transition during sarcomagenesis. / Domann, Frederick E.; Fitzgerald, Matthew P.; Gourronc, Francoise; Teoh, Melissa L.T.; Provenzano, Matthew J.; Case, Adam J.; Martin, James A.

In: Sarcoma, Vol. 2011, 598218, 28.04.2011.

Research output: Contribution to journalReview article

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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.",
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AU - Domann, Frederick E.

AU - Fitzgerald, Matthew P.

AU - Gourronc, Francoise

AU - Teoh, Melissa L.T.

AU - Provenzano, Matthew J.

AU - Case, Adam J.

AU - Martin, James A.

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N2 - 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.

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