Matrix Proteases in Health and Disease

INVASION AND INFECTION Introduction Tissue and Cell Surface Remodeling Proteases Proteases of the Blood Coagulation and the Fibrinolytic System Contact System Conclusion and Future Prospectives EXPERIMENTAL APPROACHES FOR UNDERSTANDING THE ROLE OF MATRIX METALLOPROTEINASES IN CANCER INVASION Introduction: Functional Roles of MMPs in Physiological Processes Involving the Induction and Sustaining of Cancer Invasion EMT: a Prerequisite of MMP-Mediated Cancer Invasion or a Coordinated Response to Growth-Factor-Induced MMPs? Escape from the Primary Tumor: MMP-Mediated Invasion of Basement Membranes Invasive Front Formation: Evidence for MMP Involvement In Vivo Invasion at the Leading Edge: MMP-Mediated Proteolysis of Collagenous Stroma Tumor Angiogenesis and Cancer Invasion: MMP-Mediated Interrelationships Cancer Cell Intravasation: MMP-Dependent Vascular Invasion Cancer Cell Extravasation: MMP-Dependent Invasion of the Endothelial Barrier and Subendothelial Stroma Metastatic Site: Involvement of MMPs in the Preparation, Colonization, and Invasion of Distal Organ Stroma Perspectives: MMPs in the Early Metastatic Dissemination and Awakening of Dormant Metastases PLASMINOGEN ACTIVATORS AND THEIR INHIBITORS IN CANCER Introduction The Plasminogen Activator System PROTEASE NEXIN-1 - A SERPIN WITH A POSSIBLE PROINVASIVE ROLE IN CANCER Introduction - Serpins and Cancer History of PN-1 General Biochemistry of PN-1 Inhibitory Properties of PN-1 Binding of PN-1 and PN-1-Protease Complexes to Endocytosis Receptors of the Low-Density Lipoprotein Receptor Family Pericellular Functions of PN-1 in Cell Cultures PN-1 Expression Patterns Functions of PN-1 in Normal Physiology Functions of PN-1 in Cancer Conclusions SECRETED CYSTEINE CATHEPSINS - VERSATILE PLAYERS IN EXTRACELLULAR PROTEOLYSIS Introduction Structure and Function of Cysteine Cathepsins Synthesis, Processing, and Sorting of Cysteine Cathepsins Extracellular Enzymatic Activity of Lysosomal Cathepsins Endogenous Cathepsin Inhibitors as Regulators of Extracellular Cathepsins Extracellular Substrates of Cysteine Cathepsins Cysteine Cathepsins in Cancer: Clinical Associations Cysteine Cathepsins in Cancer: Evidence from Animal Models Molecular Dysregulation of Cathepsins in Cancer Progression Extracellular Cathepsins in Cancer Conclusions and Further Directions ADAMS IN CANCER ADAMs-Multifunctional Proteins ADAMs in Tumors and Cancer Progression ADAMs in Cancer - Key Questions Yet to Be Answered The Clinical Potential of ADAMs Concluding Remarks UROKINASE-TYPE PLASMINOGEN ACTIVATOR, ITS RECEPTOR AND INHIBITOR AS BIOMARKERS IN CANCER Introduction Breast Cancer Colorectal Cancer Lung Cancer Gynecological Cancers Prostate Cancer Conclusion and Perspectives CLINICAL RELEVANCE OF MMP AND TIMP MEASUREMENTS IN CANCER TISSUE Introduction MMP Structure MMP Biology and Pathology Natural Inhibitors of MMPs Regulation of MMP Function Cancer Stromal Cell Production of MMPs Anticancer Effects of MMPs Tissue Levels of MMPs and TIMPs in Cancer Patients Conclusions NEW PROSPECTS FOR MATRIX METALLOPROTEINASE TARGETING IN CANCER THERAPY Introduction Lessons Learned from Preclinical and Clinical Studies of MMPIs in Cancer and Possible Alternatives Novel Generation of MMPIs Exploit MMP Function to Improve Drug Bioavailability Conclusion