TY - JOUR
T1 - Human chondrosarcoma cells acquire an epithelial-like gene expression pattern via an epigenetic switch
T2 - Evidence for mesenchymal-epithelial transition during sarcomagenesis
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.
PY - 2011
Y1 - 2011
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.
AB - 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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U2 - 10.1155/2011/598218
DO - 10.1155/2011/598218
M3 - Review article
C2 - 21559267
AN - SCOPUS:79955125547
SN - 1357-714X
VL - 2011
JO - Sarcoma
JF - Sarcoma
M1 - 598218
ER -