부산대학교 도서관

Contemporary fundamental investigations in the field of oncology are focused on understanding of molecule mechanisms of tumor development, progression and metastasizing. These processes involve controlled and directed proteolysis of the components of basal membrane (BM) and extracellular matrix (ECM) that is catalyzed by variety of proteolytic enzymes, including matrix metalloproteinases (MMPs). MMPs are a large family of Zn-dependent neutral endopeptidases and their basic activity is the degradation of matrix proteins. In addition they cleave diversity of non-matrix proteins, such as growth factors, signal and receptor molecules, thus modifying indirectly the cellular and tissue behavior. Based on their substrate specificity and structural organization they are subgrouped into collagenases, stromelysins, gelatinases, matrilysins, and membrane-type matrix metalloproteinases. The MMP activity is very strictly controlled at the level of gene transcription, latent zymogene activation, and inhibition by endogeneous inhibitors. MMPs are synthesized in non-active latent zymogene form (proMMPs) and are activated after secretion. The proteolytic activity of MMPs is controlled by the members of a family of anti-proteinases known as tissue inhibitors of metalloproteinases (TIMPs) and other non-specific inhibitors. The expression and activity is strictly controlled by signal transduction on the level of transcription and maturation and is affected by variety of factors, including genetic. So far, several polymorphisms in the promoter regions of MMP genes have been identified that influence the transcription activity of MMP genes and protein levels of the enzymes. The current review attempts to summarize the information about the role of MMPs and their inhibitors in development, growth, invasion, tumor angiogenesis and metastasizing of neoplastic diseases, particularly in squamous cell carcinoma of head and neck (HNSCC). [ABSTRACT FROM AUTHOR]