Cell surface activation of progelatinase A (proMMP-2) and cell migration

Gelatinase A (MMP-2) is considered to play a critical role in cell migration and invasion. The proteinase is secreted from the cell as an inactive zymogen. In vivo it is postulated that activation of progelationase A (proMMP-2) takes place on the cell surface mediated by membrane-type matrix metalloproteinases (MT-MMPs). Recent studies have demonstrated that proMMP-2 is recruited to the cell surface by interacting with tissue inhibitor of metalloproteinases-2 (TIMP-2) bound to MT1-MMP by forming a ternary complex. Free MT1-MMP closely located to the ternary complex then activates proMMP-2 on the cell surface. MT1-MMP is found in cultured invasive cancer cells at the invadopodia. The MT-MMP/TIMP-2/MMP-2 system thus provides localized expression of proteolysis of the extracellular matrix required for cell migration.