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.