title: Molecular regulation of cellular invasion--role of gelatinase A and TIMP-2.
abstract: Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell-matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Yu
authors.forename: R E
authors.initials: RE
authors.lastname: Hewitt
authors.forename: D E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: W G
authors.initials: WG
authors.lastname: Stetler-Stevenson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005109:Extracellular Matrix / Q000502:physiology*; D018093:Gelatinases / Q000235:genetics / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D011506:Proteins / Q000502:physiology*; D019716:Tissue Inhibitor of Metalloproteinase-2
chemical_list: D011506:Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2