FIGURE 5 from Small Extracellular Vesicles Promote Stiffness-mediated Metastasis

Soft EVs transform the phenotype of resident lung fibroblasts. A and B, Gene expression fold change in ACTA2, CCN2, COL1A1, IL6, KGF, MMP1, VIM, VEGFA, S100A4, S100A6, S100A10, S100A11, S100A12, S100A13, S100A14, S100A16 assessed by qRT-PCR in IMR90 human lung fibroblasts exposed to PBS only, 25 kPa EVs, and 0.5 kPa EVs. Gene expression data normalized to PBS condition. Two biological repeats. Welch ANOVA. C, Schematic showing the arrival of stiff EVs in the lung after being secreted from the primary tumor. Left panel shows a mechanically soft environment, and EVs encountering resident normal lung fibroblasts; (middle) cancer cells are then recruited to the lung; and (right) the cells, now experiencing a soft environment, release soft EVs that transform the resident fibroblasts to a CAF phenotype.