MMP Secretion Rate and Inter-invadopodia Spacing Collectively Govern Cancer Invasiveness.

摘要: Abstract Invadopodia are micron-sized invasive structures that mediate extracellular matrix (ECM) degradation through a combination of membrane-bound and soluble metalloproteinases (MMPs). However, how such localized is converted into pores big enough for cancer cells to invade, the relative contributions versus MMPs this process remain unclear. In article, we address these questions by combining experiments simulations. We show in MDA-MB-231 cells, an increase ECM density enhances invadopodia-mediated decreases inter-invadopodia spacing. mostly mediated MMPs, which activated MT1-MMP. present computational model degradation, recapitulates above observations identifies MMP secretion rate as important regulator invadopodia stability. Simulations with multiple suggest spacing collectively dictate size degraded zones. Taken together, our results creating conducive invasion, must tune density-dependent manner, thereby striking balance between penetration degradation.