Experimental Approaches for Understanding the Role of Matrix Metalloproteinases in Cancer Invasion

Clinical significance of epithelial‐mesenchymal transition

“…Vimentin, which is frequently upregulated in cells with an EMT-like phenotype, is then required for the further maturation of invadopodia [ 32 ]. Besides clearing the way for migrating tumor cells, MMPs that are released during tumor cell invasion are themselves further fueling the EMT process; the same effect is achieved via liberated TGF-β from the ECM [ 33 - 35 ]. In a mouse model of gastric cancer, it could be shown that EMT cooperates with MMP activity to gain access to lymph vessels and to spread distant metastases [ 36 ].…”

An aqueous extract from toad skin prevents gelatinase activities derived from fetal serum albumin and serum-free culture medium of human breast carcinoma MDA-MB-231 cells

“…Gelatinases are known to act in the degradation of basement membranes at the time of cancer cell migration into stromal tissues (1,2). We have previously found that toad skin extract can suppress the migration of MDA-MB-231 cells not only into a model stromal tissue constituted by type I collagen gels (16) but also into a basement membrane model tissue constituted by type IV collagen gels (unpublished data).…”

“…Carcinoma cells arise in epithelial tissues express extracellular matrix-degrading enzymes such as matrix metalloproteinases (MMPs) and invade into inner tissues while degrading basement membranes and stromal tissues (1). Of many types of MMPs, MMP-2 and -9, both of which possess gelatinase activity, are important to degrade basement membrane (1,2).…”

“…Of many types of MMPs, MMP-2 and -9, both of which possess gelatinase activity, are important to degrade basement membrane (1,2). Since the degradation of basement membrane is thought to be the initial step of metastasis, efforts to find and create compounds that can prevent gelatinase activity have proceeded (3)(4)(5)(6).…”