A MATRIX METALLOPROTEINASE EXPRESSED ON THE SURFACE OF INVASIVE TUMOR-CELLS

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 meta stasis, acting by degrading extracellular matrix macromolecules such a s type IV collagen(1-3). An inactive precursor of gelatinase A (pro-ge latinase A) is secreted and activated in invasive tumour tissue(4-7) a s a result of proteolysis which is mediated by a fraction of tumour ce ll membrane that is sensitive to metalloproteinase inhibitors(4,5). He re we report the cloning of the complementary DNA encoding a new matri x 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 recon stituted basement membrane. Tumour cells of invasive lung carcinomas, which contain activated forms of gelatinase A, were found to express t he transcript and the gene product. The new metalloproteinase may thus trigger invasion by tumour cells by activating pro-gelatinase A on th e tumour cell surface.