[Expression of matrix metalloproteinases in patients with malignant tumors].
The cancer cells secrete proteolytic enzymes, which are important in the tumor spreading. The cells must cross basement membrane and extracellular matrix barriers in order to spread. The matrix metalloproteinases are a family of endopeptidases, which enzymatic activity depends on the presence of zinc ion in the catalytic domain. Matrix metalloproteinases hydrolyze extracellular matrix components such as collagen, laminin, fibronectin, proteoglycans and contribute to the spreading of tumor cells by eliminating the surrounding extracellular matrix and basement membrane barriers. This review describes matrix metalloproteinases family classification and structure, their role under physiological conditions and induced proteolysis during pathological processes. There is a balance between proteolytic extracellular matrix degradation and proteolysis inhibition, but under pathological state (e. g. tumor development) the proteolysis becomes uncontrolled. We review tissue inhibitors of matrix metalloproteinases and synthetic matrix metalloproteinase inhibitors, their perspective in cancer treatment; as well as different matrix metalloproteinases expression in patients with tumors and its prognostic significance during cancer progression.
Stanciūte
Diana
D
Institute of Oncology, Vilnius University, Lithuania. dstanciute@hotmail.com
Didziapetriene
Janina
J
Kadziauskas
Jurgis
J
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis; D001713:Biphenyl Compounds; D002986:Clinical Trials as Topic; D004164:Diphosphonates / Q000627:therapeutic use; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000145:classification / Q000378:metabolism* / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D009930:Organic Chemicals / Q000008:administration & dosage / Q000627:therapeutic use; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D010654:Phenylbutyrates; D011379:Prognosis; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000008:administration & dosage / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D004164:Diphosphonates; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007093:Imidazoles; D061965:Matrix Metalloproteinase Inhibitors; D009930:Organic Chemicals; D010654:Phenylbutyrates; D011480:Protease Inhibitors; D013876:Thiophenes; D019714:Tissue Inhibitor of Metalloproteinases; C422302:N-((2S)-2-mercapto-1-oxo-4-(3,4,4- trimethyl-2,5-dioxo-1-imidazolidinyl)butyl)-L-leucyl-N,3- dimethyl-L-Valinamide; D010649:Phenylalanine; C113281:Bay 12-9566; C080985:batimastat; C100342:marimastat; D020782:Matrix Metalloproteinases