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A matrix metalloproteinase expressed on the surface of invasive tumour cells

Nature volume 370, pages 61–65 (1994)Cite this article

Abstract

GELATINASE A (type-IV collagenase; Mr 72,000) is produced by tumour stroma cells and is believed to be crucial for their invasion and metastasis, acting by degrading extracellular matrix macro-molecules such as type IV collagen1–3. An inactive precursor of gelatinase A (pro-gelatinase A) is secreted and activated in invasive tumour tissue4–7 as a result of proteolysis which is mediated by a fraction of tumour cell membrane that is sensitive to metallopro-teinase inhibitors4,5. Here we report the cloning of the complemen-tary DNA encoding a new matrix metalloproteinase with a potential transmembrane domain. Expression of the gene product on the cell surface induces specific activation of pro-gelatinase A in vitro and enhances cellular invasion of the reconstituted basement membrane. Tumour cells of invasive lung carcinomas, which con-tain activated forms of gelatinase A, were found to express the transcript and the gene product. The new metalloproteinase may thus trigger invasion by tumour cells by activating pro-gelatinase A on the tumour cell surface.

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Authors and Affiliations

  1. Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Takara-machi 13-1, Kanazawa, Ishikawa, 920, Japan

    Hiroshi Sato, Takahisa Takino, Jian Cao & Motoharu Seiki

  2. Department of Oral Surgery, school of Medicine, Kanazawa University, Takara-machi 13-1, Kanazawa, Ishikawa, 920, Japan

    Takahisa Takino & Etsuhide Yamamoto

  3. Department of Pathology, school of Medicine, Kanazawa University, Takara-machi 13-1, Kanazawa, Ishikawa, 920, Japan

    Yasunori Okada

  4. Department of Biochemistry, Research Institute, Fuji Chemical Industries Ltd, Takaoka, Toyama, 933, Japan

    Akira Shinagawa

Authors
  1. Hiroshi Sato
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Sato, H., Takino, T., Okada, Y. et al. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370, 61–65 (1994). https://doi.org/10.1038/370061a0

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