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Secretion of matrix metalloproteinase-2 (72 kD gelatinase/type IV collagenase = gelatinase A) by malignant human glioma cell lines: implications for the growth and cellular invasion of the extracellular matrix

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Abstract

Human glioma cells (T98G and A172 cell lines) were cultured on various extracellular matrix (ECM) components including type 1, IV and V collagens, fibronectin, laminin, and reconstituted basement membrane (Matrigel), and the role of matrix metalloproteinases (MMPs) in their growth and invasion was examined. T98G glioma cells grew well on these ECM components and invaded the reconstituted basement membrane. In contrast, A172 glioma cells showed growth inhibition on collagen types IV and V and Matrigel without invasion of the Matrigel. Gelatin zymography and enzyme immunoassays demonstrated that T98G glioma cells, but not A172 cells, secrete a large amount of matrix metallproteinase-2 (MMP-2, 72 kD gelatinase/type IV collagenase = gelatinase A), and this was confirmed by immunoblotting and immunohistochemistry. Of the two different tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), T98G cells produced only TIMP-1 during culture on Matrigel, whereas A172 cells secreted both. Although both human recombinant TIMP-1 and TIMP-2 stimulated T98G cell growth slightly on Matrigel, the in vitro invasiveness was significantly reduced by only recombinant TIMP-2. These results suggest that MMP-2 plays an important role in the ECM invasion of T98G human glioma cells in vitro.

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Authors and Affiliations

  1. Department of Neurosurgery, Fukui Medical School, Fukui, Japan

    Takao Nakagawa, Toshihiko Kubota & Masanori Kabuto

  2. Research Laboratories I, Biotechnology Section, Fuji Chemical Industries, Ltd., Takaoka, Japan

    Noboru Fujimoto

  3. Department of Molecular Immunology and Pathology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan

    Yasunori Okada

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  1. Takao Nakagawa
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  2. Toshihiko Kubota
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  3. Masanori Kabuto
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  4. Noboru Fujimoto
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  5. Yasunori Okada
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Nakagawa, T., Kubota, T., Kabuto, M. et al. Secretion of matrix metalloproteinase-2 (72 kD gelatinase/type IV collagenase = gelatinase A) by malignant human glioma cell lines: implications for the growth and cellular invasion of the extracellular matrix. J Neuro-Oncol 28, 13–24 (1996). https://doi.org/10.1007/BF00300442

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