Effect of metallothioneins on transformation of gelatinase A from human fibroblast WI-38 cells

The effect of metallothioneins (MTs) on gelatinase A activity was investigated. The collagenolytic activity of gelatinase A from human fibroblast WI-38 cells was enhanced by the addition of MTs. This enhancement may be caused by the transformation of the inactive 62 kDa intermediate species of gelatinase A to the 59 kDa active enzyme. This enhancement was also observed in the conditioned medium of WI-38 cells exposed to heavy metals, but intracellular 72 kDa pro-gelatinase A did not change. Furthermore, degradation of gelatinase A occurred in the reaction between gelatinase A with substrate and MTs. Our results suggest that MTs may be an endogenous activator of gelatinase A, and may provide a host factor in cancer metastasis.