SPP1 and neoplasm: Mechanistically, Puré highlighted a novel ECM-informed stromagenic switch – regulated by multiple factors including substratum stiffness, PDGF, TGFβ, sonic hedgehog, and osteopontin – that contributes to CAF heterogeneity and is a key component of the transition from a tumor-resistant to a tumor-permissive microenvironment [18].