Altered unfolding and stiffening of fibronectin for tumor progression

Pre-adipocytes exposed to tumor soluble factors derived from MDA-MB-231 breast cancer cells, an in vitro model of cancer-activated fibroblasts, deposited an initial extracellular matrix comprised primarily of fibronectin (Fn). This tumor-associated Fn was measured to be 87% more unfolded than that of Fn deposited by control cells and correlated to being 62% stiffer by the Förster Resonance Energy Transfer and Surface Forces Apparatus techniques, respectively. The initial dysregulated ECM lead to the rapid deposition of thick type I collagen (Col I) fibers. Our findings suggest that initial unfolded and stiff tumor-associated Fn ECMs promote altered cell-matrix interactions to fuel tumor progression.