In vitro inhibition of XXXX sarcoma cells' invasive ability by @entity71000 --a novel esteroprotease inhibitor.

@entity1 @entity5 @entity19 @entity1351 @entity1014 @entity49406 @entity71000 @entity369
@entity71000 ( @entity71000 ) is a synthetic aromatic @entity49406 compound which has a number of important biochemical effects, including inhibition of a family of esteroproteases (trypsin, urokinase, @entity1351 ) previously linked to the complex process of @entity5 invasion. Previous work has suggested that exogenous natural protease inhibitors can block invasion of @entity5 cells across basement membranes (BM) in vitro. The authors studied the effect of BABIM on the @entity1 cell line HT-1080 with the use of a quantitative in vitro amnion invasion assay system. They have verified the ability of these cells to grow in @entity19 and metastasize via the lymphatics or blood vessels on the basis of the route of administration of the inoculum. Cells which were able to actively cross the entire BM were trapped on filters and counted by both brightfield microscopy and by beta scintillation counting of cells whose DNA was labeled with tritiated @entity1014 . In agreement with either counting technique, BABIM, at a concentration of 10(-4) M, significantly inhibited invasion (P less than 0.005) over the 7-day course of the experiments. Under these conditions, the inhibitor was nontoxic and did not alter the attachment of the cells to the amniotic membrane. Furthermore, a highly significant inhibition of invasion (P less than 0.001) was also demonstrated across a variation in molar concentration of BABIM of more than 2 orders of magnitude. Most remarkably, cells were initially inhibited in their ability to invade in the presence of between 10(-9) and 10(-3) M BABIM. Measurement of Type IV specific collagenase in media from these cells shows a significant inhibition of activity in the presence of BABIM. These results suggest two, not necessarily exclusive, alternative interpretations: first, that inhibition of the proteolytic steps along the pathway of activation of basement membrane degrading enzymes results in inhibition of invasion; second, that @entity369 directed esteroproteases may work in concert with cellular collagenolytic metalloproteinases in the process of invasion by @entity1 @entity5 cells through native matrix barriers.
