Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

Christopher A Hamm; Jeff W Stevens; Hehuang Xie; Elio F Vanin; Jose A Morcuende; Hakeem Abdulkawy; Elisabeth A Seftor; Simone T Sredni; Jared M Bischof; Deli Wang; Sergey Malchenko; Maria de Fatima Bonaldo; Thomas L Casavant; Mary JC Hendrix; Marcelo B Soares

doi:10.1186/1471-2407-10-471

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Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

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Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

Christopher A Hamm, Jeff W Stevens, Hehuang Xie, Elio F Vanin, Jose A Morcuende, Hakeem Abdulkawy, Elisabeth A Seftor, Simone T Sredni, Jared M Bischof, Deli Wang, …

BMC cancer, Vol.10(1), pp.471-471

09/01/2010

DOI: 10.1186/1471-2407-10-471

PMCID: PMC2944175

PMID: 20809981

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Abstract

Background: Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established--namely, the Swarm Rat Chondrosarcoma (SRC)--and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. Methods: To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. Results: The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. Conclusion: This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis.

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Title: Subtitle: Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors
Creators: Christopher A Hamm - Interdisciplinary Graduate Program in Genetics, The University of Iowa, Iowa City, IA 52242, USA
Jeff W Stevens - Department of Orthopaedic Surgery The University of Iowa, Iowa City, Iowa 52242, USA
Hehuang Xie - Cancer Biology and Epigenomics Program, Children's Memorial Research Center
Elio F Vanin - Cancer Biology and Epigenomics Program, Children's Memorial Research Center
Jose A Morcuende - Department of Orthopaedic Surgery The University of Iowa, Iowa City, Iowa 52242, USA
Hakeem Abdulkawy - Department of Electrical and Computer Engineering, The University of Iowa, Iowa City, Iowa, USA
Elisabeth A Seftor - Cancer Biology and Epigenomics Program, Children's Memorial Research Center
Simone T Sredni - Cancer Biology and Epigenomics Program, Children's Memorial Research Center
Jared M Bischof - Cancer Biology and Epigenomics Program, Children's Memorial Research Center
Deli Wang - Biostatistics Research Core, Children's Memorial Research Center, Northwestern University's Feinberg School of Medicine, Chicago, Illinois 60614, USA
Sergey Malchenko - Cancer Biology and Epigenomics Program, Children's Memorial Research Center
Maria de Fatima Bonaldo - Cancer Biology and Epigenomics Program, Children's Memorial Research Center
Thomas L Casavant - Department of Electrical and Computer Engineering, The University of Iowa, Iowa City, Iowa, USA
Mary JC Hendrix - Cancer Biology and Epigenomics Program, Children's Memorial Research Center
Marcelo B Soares - Cancer Biology and Epigenomics Program, Children's Memorial Research Center
Resource Type: Journal article
Publication Details: BMC cancer, Vol.10(1), pp.471-471
DOI: 10.1186/1471-2407-10-471
PMID: 20809981
PMCID: PMC2944175
NLM abbreviation: BMC Cancer
ISSN: 1471-2407
eISSN: 1471-2407
Publisher: BioMed Central
Language: English
Date published: 09/01/2010
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Stead Family Department of Pediatrics; Orthopedics and Rehabilitation
Record Identifier: 9984040287002771

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