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Type I collagen is overexpressed in medulloblastoma as a component of tumor microenvironment

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Abstract

Medulloblastoma is the most common malignant brain tumor of children, and more specific and effective therapeutic management needs to be developed to improve upon existing survival rates and to avoid side-effects from current treatment. Gain of chromosome seven is the most frequent chromosome copy number aberration in medulloblastoma, suggesting that overexpression of genes on chromosome seven might be important for the pathogenesis of medulloblastoma. We used microarrays to identify chromosome seven genes overexpressed in medulloblastoma specimens, and validated using data from published gene expression datasets. The gene encoding the alpha 2 subunit of type I collagen, COL1A2, was overexpressed in all three datasets. Immunohistochemistry of tumor tissues revealed type I collagen in the leptomeninges, and in the extracellular matrix surrounding blood vessels and medulloblastoma cells. Expression of both type I collagen and the β1 subunit of integrin, a subunit of a known type I collagen receptor, localized to the same area of medulloblastoma. Adherence of D283 medulloblastoma cells to type I collagen matrix in vitro depends on the β1 subunit of integrin. Because medulloblastoma is characteristic of high vascularity, and because inhibition of type I collagen synthesis has been shown to suppress angiogenesis and tumor growth, our data suggest that type I collagen might be a potential therapeutic target for treating medulloblastoma.

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Acknowledgements

We thank the Brain Tumor Research Center Tissue Bank of UCSF for contributing tissue specimens in this study. This work was supported by funding from the Department of Neurological Surgery at UCSF, and by National Institute of General Medical Sciences training grant GM07365 (M.D.), and the Theodora B. Betz Foundation and Kyra Memorial Fund (M.A.I.). UCSF is an NCI-designated Specialized Program of Research Excellence for Brain Tumors.

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Authors and Affiliations

  1. Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, CA, 94143, USA

    Yu Liang & Nalin Gupta

  2. Division of Molecular Cell Biology, Applied Biosystems, 850 Lincoln Centre Drive, Foster City, CA, 94404, USA

    Yu Liang

  3. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Maximilian Diehn

  4. Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Maximilian Diehn

  5. Department of Pathology, University of California, San Francisco, CA, 94143, USA

    Andrew W. Bollen

  6. Departments of Pediatrics and Genetics, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH, 03756, USA

    Mark A. Israel

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  1. Yu Liang
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Correspondence to Yu Liang.

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Liang, Y., Diehn, M., Bollen, A.W. et al. Type I collagen is overexpressed in medulloblastoma as a component of tumor microenvironment. J Neurooncol 86, 133–141 (2008). https://doi.org/10.1007/s11060-007-9457-5

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  • DOI: https://doi.org/10.1007/s11060-007-9457-5

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