TGF beta 1 stimulates the secretion of matrix metalloproteinase 2 (MMP2) and the invasive behavior in human ovarian cancer cells, which is suppressedby MMP inhibitor BB3103

The present study investigated the modulatory role of transforming growth f actor beta 1 (TGF beta1) on the secretion of matrix metalloproteinases (MMP s) and tested whether the altered secretion of MMPs could directly affect t he invasive behavior of ovarian cancer cells. To this aim, human ovarian ca ncer SKOV3 cells were treated once with vehicle or various concentrations o f TGF beta1 for 24 h. Gelatinase activities in conditioned media were analy zed by zymography and densitometry. TGF beta1 dose-dependently stimulated t he secretion of a 68-kDa gelatinase, which was characterized as an MMP beca use its activity was inhibited by a metalloproteinase inhibitor 1,10-phenan throline, and by a synthetic MMP inhibitor BB3103. In addition, we used ami nophenylmercuric acetate (APMA) to activate latent gelatinases. APMA time-d ependently decreased the activity of 68-kDa gelatinase, and increased the a ctivities of 64- and 62-kDa gelatinolytic bands. The 68-kDa gelatinase was further characterized as MMP2 (gelatinase A) by immunoblotting analysis. We then tested TGF beta1 effect on the invasive potential of SKOV3 cells as a ssessed by the migration ability through reconstituted basement membrane, a nd further investigated whether TGF beta1 may act through modulating the MM P activity to affect ovarian cancer cell invasion. The results show that TG F beta1 stimulated the invasive behavior of SKOV3 cells, and that MMP inhib itor BB3103 abrogated this effect of TGF beta1. In conclusion, this study i ndicates that TGF beta1 may act partly through stimulating the secretion of MMP in promoting the invasive behavior of human ovarian cancer cells. Furt hermore, this work supports the idea that specific MMP inhibitors of the hy droxamate class could be therapeutically useful in controlling cancer cell invasion/metastasis.