In the context of the battle against cancer, the Degradome is important in three principal areas:
- Cellular proteases and their inhibitors are components of the molecular machinery of malignancy, and thus are attractive as therapeutic targets. Importantly, we now appreciate that some proteases perform functions that antagonize tumour growth, and these are then anti-targets that must be avoided
- Degradome genes are valuable as prognostic and diagnostic markers of disease that can improve the accuracy of conventional clinical and histopathological assessment
- Cellular proteases are target molecules for improving tumour detection and imaging
Section 1: The Degradome and its analysis Chapter 1: Protease Genomics and the Cancer Degradome Xose S. Puente, Gonzalo R Ordonez & Carlos López-Otín Chapter 2: The CLIP-CHIP: A focused oligonucleotide microarray platform for tranillegalscriptone analysis for the complete human and murine cancer degradomes. Rheinhild Kappelhoff, Claire H.Wilson, & Christopher M. Overall Chapter 3: The Hu/Mu ProtIn chip: A custom dual-species Oligonucleotide Microarray for profiling degradome gene expression in tumours and their microenvironment Donald R.Scwartz, Kamiar Moin, Ekkehard Weber & Bonnie F Sloane Chapter 4: Quantitative Real-Time PCR analysis of degradome gene expression Caroline J Pennington, Robert K. Nuttall, Clara Sampieri -Ramirez, , Matthew Wallard, Simon Pilgrim & Dylan R. Edwards Chapter 5: Identification of protease substrates by mass spectrometry approaches. Mari Enoksson,Wenhong Zhu & Guy Salvesen Chapter 6: Identification of protease substrates by mass spectrometry approaches – 2. Anna Prudova, Ulrich auf dem Keller & Christopher M. Overall Chapter 7: Activity based imaging and biochemical profiling tools for analysis of the cancer degradome. Vincent Dive, Margot Paulick, J.Oliver McIntyre, Lynn M. Matrisan & Matthew Bogyo. Chapter 8: Images of cleavage Kamiar Moin,Mansoureh Sameni, Christopher Jedeszko, Quanwen Li, Mary B. Olive, Raymond R. Mattingly & Bonnie F. Sloane Section 2: Insights into Protease function Chapter 9: Proteolytic pathways: Intersecting cascades in cancer development Nesrine I. Affara & Lisa M, Coussens Chapter 10: Physiological functions of plasminogen activation: Effects of gene deficiences in humans andmice Thomas H. Bugge Chapter 11: The plasminogen activation system in tissue remodelling and cancer invasion Kasper Almholt, Anna Juncker-Jensen, Kirsty Anne Green, Helene Solberg, Leif Roge Lund & John Rømer Chapter 12: The urokinase plasminogen activator receptor as a target for cancer therapy Silvia D´Alessio & Francesco Blasi Chapter 13: The endocytic collagen receptor uPARAP/Endo 180 in cancer invasion and tissue remodelling Thore Hillig, Lars H. Engelholm & Niels Behrendt Chapter 14: Physiological and pathological functions of type II transmembrane serine proteinases:Lessons from transgenic mouse models and human disease-associated mutations. Karin List & Thomas Bugge Chapter 15: Analysis of cysteine cathepsin knockout mice in cancer models Thomas Reinheckel, Vasilena Gocheva, Christoph Peters & Johanna A. Joyce Chapter 16: In vitro and in vivo models of angiogenesis to dissect MMP functions. Sarah Berndt, Françoise Bruyère, Maud Jost & Agnès Noël Chapter 17: The surface transplantation model to study the tumour-host interface Maud Jost, Silvia Vosseler, Silvia Blacher, Norbert E. Fusenig, Margareta Mueller & Agnes Noel Chapter 18: Unravelling the roles of proteases in cell migration in vitro and in vivo Jelena Gavrilovic & Xanthe Scott Chapter 19: New insights into MMP function in adipogenesis Kumari L Andarawewal & Marie-Christine Riol Chapter 20: TIMPs:Extracellular Modifiers in Cancer Development Aditya Murty,William Cruz-Munoz & Rama Khokha Section 3: The interface between Proteolysis and Cell Signalling Chapter 21: Invadopodia: Interface for Invasion Susette C Mueller, Vira V. Artym
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 tranillegalscriptomics 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.
This book covers recent knowledge of the composition of the Degradome, how it can be studied using modern approaches such as tranillegalscriptomics and mass spectrometry; and many other relevant subjects, including new approaches to targeting proteolysis for therapy.
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 tranillegalscriptomics 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.
The Degradome and Its Analysis.- Protease Genomics and the Cancer Degradome.- The CLIP-CHIP(TM): A Focused Oligonucleotide Microarray Platform for Tranillegalscriptome Analysis of the Complete Human and Murine Cancer Degradomes.- The Hu/Mu ProtIn Chip: A Custom Dual-Species Oligonucleotide Microarray for Profiling Degradome Gene Expression in Tumors and Their Microenvironment.- Quantitative Real-Time PCR Analysis of Degradome Gene Expression.- Identification of Protease Substrates by Mass Spectrometry Approaches-1.- Identification of Protease Substrates by Mass Spectrometry Approaches-2.- Activity-Based Imaging and Biochemical Profiling Tools for Analysis of the Cancer Degradome.- Images of Cleavage: Tumor Proteases in Action.- Insights into Protease Function.- Proteolytic Pathways: Intersecting Cascades in Cancer Development.- Physiological Functions of Plasminogen Activation: Effects of Gene Deficiencies in Humans and Mice.- The Plasminogen Activation System in Tissue Remodeling and Cancer Invasion.- The Urokinase Plasminogen Activator Receptor as a Target for Cancer Therapy.- The Endocytic Collagen Receptor, uPARAP/Endo180, in Cancer Invasion and Tissue Remodeling.- Physiological and Pathological Functions of Type II Transmembrane Serine Proteases: Lessons from Transgenic Mouse Models and Human Disease-Associated Mutations.- Roles of Cysteine Proteases in Tumor Progression: Analysis of Cysteine Cathepsin Knockout Mice in Cancer Models.- In Vitro and In Vivo Models of Angiogenesis to Dissect MMP Functions.- The Surface Transplantation Model to Study the Tumor-Host Interface.- Unravelling the Roles of Proteinases in Cell Migration In Vitro and In Vivo.- New Insights into MMP function in Adipogenesis.- TIMPs: Extracellular Modifiers in Cancer Development.- The InterfaceBetween Proteolysis and Cell Signalling.- Invadopodia: Interface for Invasion.- uPAR and Proteases in Mobilization of Hematopoietic Stem Cells.- The Urokinase Receptor and Integrins Constitute a Cell Migration Signalosome.- Measuring uPAR Dynamics in Live Cells.- Janus-Faced Effects of Broad-Spectrum and Specific MMP Inhibition on Metastasis.- Cytokine Substrates: MMP Regulation of Inflammatory Signaling Molecules.- Matrix Metalloproteinases as Key Regulators of Tumor-Bone Interaction.- The Degradome as Source of Cancer Diagnostic and Markers.- The Plasminogen Activation System as a Source of Prognostic Markers in Cancer.- Cysteine Cathepsins and Cystatins as Cancer Biomarkers.- Novel Degradome Markers in Breast Cancer.- Meta-Analysis of Gene Expression Microarray Data: Degradome Genes in Healthy and Cancer Tissues.- Degradome Gene Polymorphisms.- TIMP-1 as a Prognostic Marker in Colorectal Cancer.- Novel Therapeutic Strategies.- Structure and Inhibition of the Urokinase-Type Plasminogen Activator Receptor.- Engineered Antagonists of uPA and PAI-1.- MMP Inhibitor Clinical Trials - The Past, Present, and Future.- Tailoring TIMPs for Selective Metalloproteinase Inhibition.- Third-Generation MMP Inhibitors: Recent Advances in the Development of Highly Selective Inhibitors.- Protease-Activated Delivery and Imaging Systems.- Development of Tumour-Selective and Endoprotease-Activated Anticancer Therapeutics.- Targeting Degradome Genes via Engineered Viral Vectors.
Inhaltsverzeichnis
The Degradome and Its Analysis.- Protease Genomics and the Cancer Degradome.- The CLIP-CHIP(TM): A Focused Oligonucleotide Microarray Platform for Tranillegalscriptome Analysis of the Complete Human and Murine Cancer Degradomes.- The Hu/Mu ProtIn Chip: A Custom Dual-Species Oligonucleotide Microarray for Profiling Degradome Gene Expression in Tumors and Their Microenvironment.- Quantitative Real-Time PCR Analysis of Degradome Gene Expression.- Identification of Protease Substrates by Mass Spectrometry Approaches-1.- Identification of Protease Substrates by Mass Spectrometry Approaches-2.- Activity-Based Imaging and Biochemical Profiling Tools for Analysis of the Cancer Degradome.- Images of Cleavage: Tumor Proteases in Action.- Insights into Protease Function.- Proteolytic Pathways: Intersecting Cascades in Cancer Development.- Physiological Functions of Plasminogen Activation: Effects of Gene Deficiencies in Humans and Mice.- The Plasminogen Activation System in Tissue Remodeling and Cancer Invasion.- The Urokinase Plasminogen Activator Receptor as a Target for Cancer Therapy.- The Endocytic Collagen Receptor, uPARAP/Endo180, in Cancer Invasion and Tissue Remodeling.- Physiological and Pathological Functions of Type II Transmembrane Serine Proteases: Lessons from Transgenic Mouse Models and Human Disease-Associated Mutations.- Roles of Cysteine Proteases in Tumor Progression: Analysis of Cysteine Cathepsin Knockout Mice in Cancer Models.- In Vitro and In Vivo Models of Angiogenesis to Dissect MMP Functions.- The Surface Transplantation Model to Study the Tumor-Host Interface.- Unravelling the Roles of Proteinases in Cell Migration In Vitro and In Vivo.- New Insights into MMP function in Adipogenesis.- TIMPs: Extracellular Modifiers in Cancer Development.- The InterfaceBetween Proteolysis and Cell Signalling.- Invadopodia: Interface for Invasion.- uPAR and Proteases in Mobilization of Hematopoietic Stem Cells.- The Urokinase Receptor and Integrins Constitute a Cell Migration Signalosome.- Measuring uPAR Dynamics in Live Cells.- Janus-Faced Effects of Broad-Spectrum and Specific MMP Inhibition on Metastasis.- Cytokine Substrates: MMP Regulation of Inflammatory Signaling Molecules.- Matrix Metalloproteinases as Key Regulators of Tumor-Bone Interaction.- The Degradome as Source of Cancer Diagnostic and Markers.- The Plasminogen Activation System as a Source of Prognostic Markers in Cancer.- Cysteine Cathepsins and Cystatins as Cancer Biomarkers.- Novel Degradome Markers in Breast Cancer.- Meta-Analysis of Gene Expression Microarray Data: Degradome Genes in Healthy and Cancer Tissues.- Degradome Gene Polymorphisms.- TIMP-1 as a Prognostic Marker in Colorectal Cancer.- Novel Therapeutic Strategies.- Structure and Inhibition of the Urokinase-Type Plasminogen Activator Receptor.- Engineered Antagonists of uPA and PAI-1.- MMP Inhibitor Clinical Trials - The Past, Present, and Future.- Tailoring TIMPs for Selective Metalloproteinase Inhibition.- Third-Generation MMP Inhibitors: Recent Advances in the Development of Highly Selective Inhibitors.- Protease-Activated Delivery and Imaging Systems.- Development of Tumour-Selective and Endoprotease-Activated Anticancer Therapeutics.- Targeting Degradome Genes via Engineered Viral Vectors.
Klappentext
Proteolysis is essential for life. From the breakdown of proteins in food for biosynthesis, through to antigen processing in the immune system, the blood cl- ting cascade, and the hormone-regulated remodelling of female reproductive tissues in adult mammals - proteolysis governs functionality, homeostasis, and fate at the levels of the cell and the entire organism. For the cancer cell, intracellular prote- ysis carried out by caspases and the proteasome must be enlisted and controlled to allow it to escape apoptosis. Functioning on the cancer cell surface or in the extracellular milieu, secreted proteases (primarily metalloproteinases, serine p- teases, and cathepsins) determine the interactions of cells with their environments. Once considered simply as promoting tumour cell invasion through tissue barriers, proteolysis is now known to be integral to many aspects of cancer biology, including angiogenesis, regulation of the bioavailability of growth factors, cellular adhesion, cytokine/chemokine signalling, in?ammatory cell recruitment, and the mobilization of normal cells from their tissue compartments to act as accomplices in metastasis. The last decade has witnessed a revolution in our thinking concerning the role of extracellular proteolysis in cancer biology: this is the primary focus of this book.
In the context of the battle against cancer, the Degradome is important in three principal areas:
Cellular proteases and their inhibitors are components of the molecular machinery of malignancy, and thus are attractive as therapeutic targets. Importantly, we now appreciate that some proteases perform functions that antagonize tumour growth, and these are then anti-targets that must be avoided
Degradome genes are valuable as prognostic and diagnostic markers of disease that can improve the accuracy of conventional clinical and histopathological assessment
Cellular proteases are target molecules for improving tumour detection and imaging
