Furthermore, crotoxinremodeling of the tumor microenvironment by regulating TGF‐β1 activation, viainhibition of MMP‐9 and αv integrin secretion in MRC‐5/A549 spheroids and byinhibiting MMP‐13 secretion, which activates MMP‐9; both actions are associated withreduced metastasis and invasion [53].Finally, the presence of crotoxin in MRC-5/A549 spheroids markedly inhibits thebinding of chemokines to their receptors, processes linked to proliferation,migration, invasion, and epithelial-mesenchymal transition in various cancer celllines [53]. This evidence concerns the gene MMP13 and cancer.