A matrix metalloproteinase expressed on the surface of invasive tumour cells

Abstract

GELATINASE A (type-IV collagenase; M_r 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 collagen^1–3. 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.