tailieunhanh - Báo cáo khoa học: Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting

Matrix metalloproteinases (MMPs) consist of a multigene family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases implicated in pathological processes, such as carcinogenesis. In this regard, their activity plays a pivotal role in tumor growth and the multistep processes of invasion and metastasis, including proteolytic degradation of ECM | 1FEBS Journal MINIREVIEW Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting Chrisostomi Gialeli1 Achilleas D. Theocharis1 and Nikos K. Karamanos1 2 1 Department of Chemistry Laboratory of Biochemistry University of Patras Greece 2 Institute of ChemicalEngineering and High-Temperature ChemicalProcesses FORTH ICE-HT Patras Greece Keywords angiogenesis invasion and metastasis matrix metalloproteinase matrix metalloproteinase inhibitor pharmacological target Correspondence N. Karamanos Laboratory of Biochemistry Department of Chemistry University of Patras 26110 Patras Greece Fax 30 2610 997153 Tel 30 2610 997915 E-mail Received 20 June 2010 revised 20 August 2010 accepted 18 October 2010 doi Matrix metalloproteinases MMPs consist of a multigene family of zincdependent extracellular matrix ECM remodeling endopeptidases implicated in pathological processes such as carcinogenesis. In this regard their activity plays a pivotal role in tumor growth and the multistep processes of invasion and metastasis including proteolytic degradation of ECM alteration of the cell-cell and cell-ECM interactions migration and angiogenesis. The underlying premise of the current minireview is that MMPs are able to proteolyti-cally process substrates in the extracellular milieu and in so doing promote tumor progression. However certain members of the MMP family exert contradicting roles at different stages during cancer progression depending among other factors on the tumor stage tumor site enzyme localization and substrate profile. MMPs are therefore amenable to therapeutic intervention by synthetic and natural inhibitors providing perspectives for future studies. Multiple therapeutic agents called matrix metalloproteinase inhibitors MMPIs have been developed to target MMPs attempting to control their enzymatic activity. Even though clinical trials with these compounds do not show the expected