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.
Author(s): Xose S. Puente, Gonzalo R. Ordóñez, Carlos López-Otín (auth.), Dylan Edwards, Gunilla Høyer-Hansen, Francesco Blasi, Bonnie F. Sloane (eds.)
Edition: 1
Publisher: Springer-Verlag New York
Year: 2008
Language: English
Pages: 926
Tags: Cancer Research; Human Genetics; Medical Microbiology; Immunology; Virology; Molecular Medicine
Front Matter....Pages i-xxiii
Protease Genomics and the Cancer Degradome....Pages 3-15
The CLIP-CHIP™: 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
