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.
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.
