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Products of cells from gliomas: IX. Evidence that two fundamentally different mechanisms change extracellular matrix expression by gliomas

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Four human astrocytic gliomas of high grade of malignancy were each evaluated in tissue andin vitro for percentages of cells expressing glial fibrillary acidic protein (GFAP), collagen type IV, laminin and fibronectin assessed by immunofluorescence with counterstaining of nuclear DNA. Percentages of cells with reticulin and cells binding fluorescein-labeledUlex europaeus agglutinin were also assessed. In tissue, each extracellular matrix (ECM) component was associated with cells in the walls of abnormal proliferations of glioma vessels, and all four tumors had the same staining pattern. Two strikingly different patterns of conversion of gene product expression emerged duringin vitro cultivation. (1). In the most common pattern, percentages of all six markers consistently shifted toward the exact phenotype of mesenchymal cells in abnormal vascular proliferations: increased reticulin, collagen type IV, laminin and fibronectin; markedly decreased glial marker GFAP and absent endothelial markerUlex europaeus agglutinin. The simplest explanation of this constellation of changes coordinated toward expression of vascular ECM markers is that primary glioma cell cultures are overgrown by mesenchymal cells from the abnormal vascular proliferations of the original glioma. These cell cultures were tested forin situ hybridization (ISH) signals of chromosomes 7 and 10. Cells from one glioma had diploid signals. Cells from the other glioma had aneuploid signals indicating they were neoplastic; however, their signals reflected different numerical chromosomal aberrations than those common to neoplastic glia. (2). The second pattern was different. Cells with ISH chromosomal signals of neoplastic glia retained GFAP, and gained collagen type IV. Their laminin and fibronectin diminished, but persisted among a lower percentage of cells. Cloning and double immunofluorescence confirmed the presence of individual cells with glial and mesenchymal markers. A cell expressing GFAP in addition to either fibronectin, reticulin or collagen type IV is not a known constituent of glioblastoma tissue. This provides evidence of a second mechanism of conversion of gene expression in gliomas.

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Authors and Affiliations

  1. The Department of Pathology, The University of Michigan Medical School, 48109, Ann Arbor, MI, USA

    Paul E. McKeever, James Varani & M. Wang

  2. The Department of Surgery, The University of Michigan Medical School, 48109, Ann Arbor, MI, USA

    Stephen M. Papadopoulos

  3. The Department of Pediatrics, The University of Medicine and Dentistry of New Jersey, 08103, Camden, NJ, USA

    J. Philip McCoy

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  1. Paul E. McKeever
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  2. James Varani
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  4. M. Wang
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  5. J. Philip McCoy
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McKeever, P.E., Varani, J., Papadopoulos, S.M. et al. Products of cells from gliomas: IX. Evidence that two fundamentally different mechanisms change extracellular matrix expression by gliomas. J Neuro-Oncol 24, 267–279 (1995). https://doi.org/10.1007/BF01052843

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