SPARC and neoplasm: This study shows that cath-D secreted by TNBC cells triggers fibroblast- and cancer cell-derived SPARC cleavage at the acidic pH of the tumor microenvironment, leading to the production of the bioactive 9-kDa C-terminal SPARC fragment that inhibits cancer cell adhesion and spreading on fibronectin, and stimulates their migration, endothelial transmigration and invasion (Figure 9).