Journal article
Large-scale molecular comparison of human schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues
Cancer research (Chicago, Ill.), Vol.66(5), pp.2584-2591
2006
DOI: 10.1158/0008-5472.CAN-05-3330
PMID: 16510576
Abstract
Malignant peripheral nerve sheath tumors (MPNST) are highly invasive soft tissue sarcomas that arise within the peripheral nerve and frequently metastasize. To identify molecular events contributing to malignant transformation in peripheral nerve, we compared eight cell lines derived from MPNSTs and seven normal human Schwann cell samples. We found that MPNST lines are heterogeneous in their in vitro growth rates and exhibit diverse alterations in expression of pRb, p53, p14Arf, and p16INK4a proteins. All MPNST cell lines express the epidermal growth factor receptor and lack S100β protein. Global gene expression profiling using Affymetrix oligonucleotide microarrays identified a 159-gene molecular signature distinguishing MPNST cell lines from normal Schwann cells, which was validated in Affymetrix microarray data generated from 45 primary MPNSTs. Expression of Schwann cell differentiation markers (SOX10, CNP, PMP22, and NGFR) was down-regulated in MPNSTs whereas neural crest stem cell markers, SOX9 and TWIST1, were overexpressed in MPNSTs. Previous studies have implicated TWIST1 in apoptosis inhibition, resistance to chemotherapy, and metastasis. Reducing TWIST1 expression in MPNST cells using small interfering RNA did not affect apoptosis or chemoresistance but inhibited cell chemotaxis. Our results highlight the use of gene expression profiling in identifying genes and molecular pathways that are potential biomarkers and/or therapeutic targets for treatment of MPNST and support the use of the MPNST cell lines as a primary analytic tool.
Details
- Title: Subtitle
- Large-scale molecular comparison of human schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues
- Creators
- Shyra J MILLER - Division of Experimental Hematology, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio, United StatesFatima RANGWALA - Division of Experimental Hematology, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio, United StatesVictor MAUTNER - Department of Neurosurgery, University Clinic Hamburg-Eppendorf, Hamburg, GermanyMeena UPADHYAYA - Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, United KingdomDavid MUIR - Department of Pediatric Neurology, Neuroscience, University of Florida, Gainesville, Florida, United StatesMargaret WALLACE - Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United StatesJussara HAGEN - Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa, United StatesDawn E QUELLE - Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa, United StatesMark A WATSON - Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United StatesArie PERRY - Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United StatesDavid H GUTMANN - Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United StatesNancy RATNER - Division of Experimental Hematology, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio, United StatesJon WILLIAMS - Division of Experimental Hematology, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio, United StatesPeter ACKERMAN - Division of Experimental Hematology, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio, United StatesSue KONG - Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio, United StatesAnil G JEGGA - Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio, United StatesSergio KAISER - Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio, United StatesBruce J ARONOW - Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio, United StatesSilke FRAHM - Department of Neurosurgery, University Clinic Hamburg-Eppendorf, Hamburg, GermanyLan KLUWE - Department of Neurosurgery, University Clinic Hamburg-Eppendorf, Hamburg, Germany
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.66(5), pp.2584-2591
- Publisher
- American Association for Cancer Research; Philadelphia, PA
- DOI
- 10.1158/0008-5472.CAN-05-3330
- PMID
- 16510576
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 2006
- Academic Unit
- Molecular Physiology and Biophysics; Pathology; Neuroscience and Pharmacology
- Record Identifier
- 9984040492602771
Metrics
19 Record Views