The cancer degradome: proteases and cancer biology / Dylan Edwards ... [et al.], editors

Proteases that act in the extracellular environment have been historically associated with tumorigenesis and metastasis by virtue of their ability to carry out "path-clearing" for cancer cells. In the past few years it has become clear that they also shape the pericellular signaling environment, with profound consequences for cell fate and phenotype in both normal development and disease states. The repertoire of proteases that cells and tissues coordinately regulate in order to modulate their local environment is the **DEGRADOME** – which in humans is represented by at least 569 proteases in five catalytic classes. "__The Cancer Degradome: Proteases in Cancer Biology__" , edited by Dylan Edwards, Francesco Blasi, Gunilla-Høyer-Hansen and Bonnie Sloane, covers recent knowledge of the composition of the Degradome, how it can be studied using modern approaches such as transcriptomics and mass spectrometry; how protease activity can be imaged both __in vitro__ and __in vivo__; how gene knockout mice have improved our knowledge of the roles of proteases in cancer; the links that have emerged between proteolysis and cell signaling; how the Degradome can be a useful source of diagnostic and prognostic markers; and finally new approaches to target proteolysis for therapy. Front Matter....Pages i-xxiii Protease Genomics and the Cancer Degradome....Pages 3-15 The CLIP-CHIPTM: A Focused Oligonucleotide Microarray Platform for Transcriptome Analysis of the Complete Human and Murine Cancer Degradomes....Pages 17-35 The Hu/Mu ProtIn Chip: A Custom Dual-Species Oligonucleotide Microarray for Profiling Degradome Gene Expression in Tumors and Their Microenvironment....Pages 37-47 Quantitative Real-Time PCR Analysis of Degradome Gene Expression....Pages 49-65 Identification of Protease Substrates by Mass Spectrometry Approaches-1....Pages 67-82 Identification of Protease Substrates by Mass Spectrometry Approaches-2....Pages 83-100 Activity-Based Imaging and Biochemical Profiling Tools for Analysis of the Cancer Degradome....Pages 101-135 Images of Cleavage: Tumor Proteases in Action....Pages 137-154 Proteolytic Pathways: Intersecting Cascades in Cancer Development....Pages 157-182 Physiological Functions of Plasminogen Activation: Effects of Gene Deficiencies in Humans and Mice....Pages 183-201 The Plasminogen Activation System in Tissue Remodeling and Cancer Invasion....Pages 203-221 The Urokinase Plasminogen Activator Receptor as a Target for Cancer Therapy....Pages 223-243 The Endocytic Collagen Receptor, uPARAP/Endo180, in Cancer Invasion and Tissue Remodeling....Pages 245-258 Physiological and Pathological Functions of Type II Transmembrane Serine Proteases: Lessons from Transgenic Mouse Models and Human Disease-Associated Mutations....Pages 259-279 Roles of Cysteine Proteases in Tumor Progression: Analysis of Cysteine Cathepsin Knockout Mice in Cancer Models....Pages 281-304 In Vitro and In Vivo Models of Angiogenesis to Dissect MMP Functions....Pages 305-325 The Surface Transplantation Model to Study the Tumor–Host Interface....Pages 327-342 Unravelling the Roles of Proteinases in Cell Migration In Vitro and In Vivo....Pages 343-360 New Insights into MMP function in Adipogenesis....Pages 361-372 TIMPs: Extracellular Modifiers in Cancer Development....Pages 373-400 Invadopodia: Interface for Invasion....Pages 403-431 uPAR and Proteases in Mobilization of Hematopoietic Stem Cells....Pages 433-450 The Urokinase Receptor and Integrins Constitute a Cell Migration Signalosome....Pages 451-474 Measuring uPAR Dynamics in Live Cells....Pages 475-493 Janus-Faced Effects of Broad-Spectrum and Specific MMP Inhibition on Metastasis....Pages 495-517 Cytokine Substrates: MMP Regulation of Inflammatory Signaling Molecules....Pages 519-539 Matrix Metalloproteinases as Key Regulators of Tumor–Bone Interaction....Pages 541-566 The Plasminogen Activation System as a Source of Prognostic Markers in Cancer....Pages 569-586 Cysteine Cathepsins and Cystatins as Cancer Biomarkers....Pages 587-625 Novel Degradome Markers in Breast Cancer....Pages 627-643 Meta-Analysis of Gene Expression Microarray Data: Degradome Genes in Healthy and Cancer Tissues....Pages 645-661 Degradome Gene Polymorphisms....Pages 663-677 TIMP-1 as a Prognostic Marker in Colorectal Cancer....Pages 679-696 Structure and Inhibition of the Urokinase-Type Plasminogen Activator Receptor....Pages 699-719 Engineered Antagonists of uPA and PAI-1....Pages 721-758 MMP Inhibitor Clinical Trials – The Past, Present, and Future....Pages 759-785 Tailoring TIMPs for Selective Metalloproteinase Inhibition....Pages 787-810 Third-Generation MMP Inhibitors: Recent Advances in the Development of Highly Selective Inhibitors....Pages 811-825 Protease-Activated Delivery and Imaging Systems....Pages 827-851 Development of Tumour-Selective and Endoprotease-Activated Anticancer Therapeutics....Pages 853-876 Targeting Degradome Genes via Engineered Viral Vectors....Pages 877-894 Back Matter....Pages 895-926

this Book Will Aim To Cover Recent Knowledge Of The Composition Of The Degradome, How It Can Be Studied Using Modern Approaches Such As Transcriptomics And Mass Spectrometry; How Gene Knockout Mice Have Improved Our Knowledge Of The Roles Of Proteases In Cancer; How Their Activity Can Be Imaged Both In Vitro And In Vivo; The Links That Have Emerged Between Proteolysis And Cell Signalling; How The Degradome Can Be A Useful Source Of Diagnostic And Prognostic Markers; And Finally New Approaches To Targeting Proteolysis For Therapy.

This book covers recent knowledge of the composition of the degradome, how it can be studied using modern approaches such as transcriptomics and mass spectrometry; how gene knockout mice have improved our knowledge of the roles of proteases in cancer; how their activity can be imaged both in vitro and in vivo; the links that have emerged between proteolysis and cell signalling; how the degradome can be a useful source of diagnostic and prognostic markers; and finally new approaches to targeting proteolysis for therapy This book covers recent knowledge of the composition of the Degradome, how it can be studied using modern approaches such as transcriptomics and mass spectrometry; and many other relevant subjects, including new approaches to targeting proteolysis for therapy.