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.

Section 1: The Degradome and its analysis Chapter 1: Protease Genomics and the Cancer Degradome Xose S. Puente, Gonzalo R Ordonez & Carlos Lopez-Otin Chapter 2: The CLIP-CHIP: A focused oligonucleotide microarray platform for transcriptone 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 Romer 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, Francoise Bruyere, Maud Jost & Agnes Noel 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