Synergistic effect of blocking XXXX cell invasion revealed by computer simulations.

@entity1 @entity1476 @entity5 @entity1551 @entity3 @entity204
Invasion and @entity3 are the main cause of @entity204 in @entity5 @entity1 . The initial step of invasion is the degradation of extracellular matrix (ECM) by primary @entity5 cells in a tissue. Membranous metalloproteinase @entity1551 and soluble metalloproteinase @entity1476 are thought to play an important role in the degradation of ECM. In the previous report, we found that the repetitive insertion of @entity1551 to invadopodia was crucial for the effective degradation of ECM (Hoshino, D., et al., PLoS Comp. Biol., 2012, e1002479). However, the role of @entity1476 and the effect of inhibitors for these ECM-degrading proteases were still obscure. Here we investigated these two problems by using the same model as in the previous report. First we tested the effect of @entity1476 and found that while @entity1551 played a major role in the degradation of ECM, @entity1476 played only a marginal effect on the degradation of ECM. Based on these findings, we next tested the effect of a putative inhibitor for @entity1551 and found that such inhibitor was ineffective in blocking ECM degradation. Then we tested combined strategy including inhibitor for @entity1551 , reduction of its turnover and its content in vesicles. A synergistic effect of combined strategy was observed in the decrease in the efficacy of ECM degradation. Our simulation study suggests the importance of combined strategy in blocking @entity5 invasion and @entity3 .
