A matrix metalloproteinase expressed on the surface of invasive tumour cells

Hiroshi Sato, Takahisa Takino, Yasunori Okada, Jian Cao, Akira Shinagawa, Etsuhide Yamamoto, Motoharu Seiki

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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 tissue 4-7 as a result of proteolysis which is mediated by a fraction of tumour cell membrane that is sensitive to metallopro-teinase inhibitors 4,5. 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.

Original languageEnglish
Pages (from-to)61-65
Number of pages5
JournalNature
Volume370
Issue number6484
DOIs
Publication statusPublished - 1994

ASJC Scopus subject areas

  • General

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    Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E., & Seiki, M. (1994). A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature, 370(6484), 61-65. https://doi.org/10.1038/370061a0