Proteolytic and non-proteolytic regulation of collective cell invasion: tuning by ECM density and organization.

ABSTRACT: Cancer cells manoeuvre through extracellular matrices (ECMs) using different invasion modes, including single cell and collective cell invasion. These modes rely on MMP-driven ECM proteolysis to make space for cells to move. How cancer-associated alterations in ECM influence the mode of invasion remains unclear. Further, the sensitivity of the two invasion modes to MMP dynamics remains unexplored. In this paper, we address these open questions using a multiscale hybrid computational model combining ECM density-dependent MMP secretion, MMP diffusion, ECM degradation by MMP and active cell motility. Our results demonstrate that in randomly aligned matrices, collective cell invasion is more efficient than single cell invasion. Although increase in MMP secretion rate enhances invasiveness inde

SUBMITTER: Kumar S 

PROVIDER: S-EPMC4735823 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature