EFFECT OF METALLOTHIONEINS ON COLLAGENOLYTIC ACTIVITY OF TUMOR GELATINASE-B

The effect of metallothioneins (MTs) on the collagenolytic activity of tumor pro-gelatinase B (92 kDa type IV collagenase, Matrix metallopro teinase-9, MMP-9) was investigated. The activity of progelatinase B pu rified from conditioned medium of human fibrosarcoma HT-1080 cells was enhanced in a concentration- and time-dependent fashion by addition o f metallothioneins (MTs), purified from livers of CdCl2 treated male W istar rats but not by addition of zinc or cadmium as binding metals. T his MTs enhancing effect was not observed on experimentally activated gelatinase B. These results suggest that MTs act by converting latent enzyme to active form. Activation of progelatinase B by rat Cd MTs occ urred repidly, but this reaction was incomplete and may have been reve rsible, Complete activation of pro-gelatinase B, however quickly progr essed in the presence of substrate. The MTs, on the other hand, did no t change, which was demonstrated by tricine-SDS-PAGE analysis. The res ults suggest that MTs may be endogenous activators of pro-gelatinase B and could be host factors related to cancer cell invasion and metasta sis and to inflammatory disease.