Human Chondrosarcoma Cells Acquire an Epithelial-Like Gene Expression Pattern via an Epigenetic Switch: Evidence for Mesenchymal-Epithelial Transition during Sarcomagenesis

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

doi:10.1155/2011/598218

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Human Chondrosarcoma Cells Acquire an Epithelial-Like Gene Expression Pattern via an Epigenetic Switch: Evidence for Mesenchymal-Epithelial Transition during Sarcomagenesis

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Human Chondrosarcoma Cells Acquire an Epithelial-Like Gene Expression Pattern via an Epigenetic Switch: Evidence for Mesenchymal-Epithelial Transition during Sarcomagenesis

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

Sarcoma, Vol.2011, pp.1-11

2011

DOI: 10.1155/2011/598218

PMCID: PMC3087947

PMID: 21559267

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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, and14-3-3σ, all of which are governed epigenetically through cytosine methylation. Indeed, loss of cytosine methylation was tightly associated with acquired expression of bothmaspinand14-3-3σin chondrosarcomas. In contrast, chondrocyte cells were negative formaspinand14-3-3σand 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 factorsnailwhich has been reported to be an important mediator of epithelial to mesenchymal transitions (EMTs). In chondrosarcoma cellssnailis downregulated suggesting a role for loss ofsnailexpression 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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Title: Subtitle: Human Chondrosarcoma Cells Acquire an Epithelial-Like Gene Expression Pattern via an Epigenetic Switch: Evidence for Mesenchymal-Epithelial Transition during Sarcomagenesis
Creators: Matthew P Fitzgerald - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA
Francoise Gourronc - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA
Melissa L. T Teoh - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA
Matthew J Provenzano - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
Adam J Case - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA
James A Martin - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA
Frederick E Domann - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Sarcoma, Vol.2011, pp.1-11
DOI: 10.1155/2011/598218
PMID: 21559267
PMCID: PMC3087947
NLM abbreviation: Sarcoma
ISSN: 1357-714X
eISSN: 1369-1643
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 CA73612, R01 CA115438
Language: English
Date published: 2011
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Microbiology and Immunology; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Surgery; Radiation Oncology
Record Identifier: 9984040237402771

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