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Stromal cells are prominent in solid tumor microenvironments and contribute to tumor progression. In particular, fibroblasts are common cell types in the tumor stroma that play important roles in remodeling the extracellular matrix (ECM). Here, we perform co-culture experiments with tumor cells and fibroblasts embedded in 3D collagen I matrices. We investigate the impact of fibroblasts on the migratory behavior of neighboring tumor cells and on the evolution of the surrounding ECM. We find that fibroblasts increase tumor cell motility and facilitate the transition from confined to diffusive tumor cell motions, indicative of an uncaging effect. Furthermore, the ECM is globally and locally remodeled substantially with the presence of fibroblasts. Moreover, these fibroblast-mediated phenomena are in part dependent on matrix metalloproteinases.

Fibroblast-mediated uncaging of cancer cells and dynamic evolution of the physical microenvironment