A matrix metalloproteinase expressed on the surface of invasive tumour cells

H Sato, T Takino, Y Okada, J Cao, A Shinagawa… - Nature, 1994 - nature.com
H Sato, T Takino, Y Okada, J Cao, A Shinagawa, E Yamamoto, M Seiki
Nature, 1994nature.com
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 …
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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