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    Osteopontin expression in intratumoral astrocytes marks tumor progression in gliomas induced by prenatal exposure to N-ethyl-N-nitrosourea

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    Authors
    Jang, Taichang
    Savarese, Todd M.
    Low, Hoi Pang
    Kim, Sunchin
    Vogel, Hannes
    Lapointe, David S.
    Duong, Timothy Q.
    Litofsky, N. Scott
    Weimann, James M.
    Ross, Alonzo H.
    Recht, Lawrence D.
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    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Department of Cell Biology
    Information Services
    Department of Cancer Biology
    Department of Neurology
    Document Type
    Journal Article
    Publication Date
    2006-05-03
    Keywords
    Animals
    Astrocytes
    Cerebral Cortex
    Disease Models, Animal
    Disease Progression
    Ethylnitrosourea
    Female
    Gene Expression Profiling
    *Gene Expression Regulation, Neoplastic
    Glioma
    Immunohistochemistry
    Intermediate Filament Proteins
    Nerve Tissue Proteins
    Osteopontin
    Pregnancy
    *Pregnancy, Animal
    Prenatal Exposure Delayed Effects
    Rats
    Rats, Sprague-Dawley
    Sialoglycoproteins
    Time Factors
    Transfection
    Tumor Markers, Biological
    Cancer Biology
    Molecular and Cellular Neuroscience
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    Link to Full Text
    http://www.sciencedirect.com/science/article/pii/S000294401062189X
    Abstract
    To better study early events in glioma genesis, markers that reliably denote landmarks in glioma development are needed. In the present study, we used microarray analysis to compare the gene expression patterns of magnetic resonance imaging (MRI)-localized N-ethyl-N-nitrosourea (ENU)-induced tumors in rat brains with those of uninvolved contralateral side and normal brains. Our analysis identified osteopontin (OPN) as the most up-regulated gene in glioma. Using immunohistochemistry we then confirmed OPN expression in every tumor examined (n = 17), including those with diameters as small as 300 mum. By contrast, no OPN immunostaining was seen in normal brain or in brains removed from ENU-exposed rats before the development of glioma. Further studies confirmed that OPN was co-localized exclusively in intratumoral glial fibrillary acidic protein-expressing cells and was notably absent from nestin-expressing ones. In conjunction with this, we confirmed that both normal neurosphere cells and ENU-im-mortalized subventricular zone/striatal cells produced negligible amounts of OPN compared to the established rat glioma cell line C6. Furthermore, inducing OPN expression in an immortalized cell line increased cell proliferation. Based on these findings, we conclude that OPN overexpression in ENU-induced gliomas occurs within a specific subset of intratumoral glial fibrillary acidic protein-positive cells and becomes evident at the stage of tumor progression.
    Source
    Am J Pathol. 2006 May;168(5):1676-85.
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/37645
    PubMed ID
    16651633
    Related Resources
    Link to Article in PubMed
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    UMass Chan Faculty and Researcher Publications

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