This study covers the sequence information, three-dimensional structures, activation, protein substrates, specificity requirements, inhibition, and biological roles of identified MMPs.

The biochemistry and cell biology of Matrix Metalloproteinases (MMPs) are not necessarily straightforward, but basic information on the history of these enzymes, their various functions that extend far beyond the cleaving of the extracellular matrix, and the complex mechanisms that control their expression are valuable to both scientists and clinicians. This volume summarizes the salient features and functions of MMPs and applies this information in a practical manner in order to understand how they contribute to normal physiology and pathology of selected diseases. Chapters by noted clinicians Jean-Michel Dayer, MD in rheumatology, Jian Cao, MD in oncology, and Peter Libby, MD in cardiology, represent important practical and clinically-oriented contributions.

The chapters in this book thoroughly cover the structure, regulation, and function of matrix metalloproteinases, and provide information on the latest strategies to inhibit enzyme activity. This work will be an indispensable reference tool for investigators with an interest in extracellular matrix biology, matrix turnover, enzymology and biochemistry of proteinases, developmental biology, pathology, and therapeutic interventions. Provides state-of-the-art information on a field with broad implications to many areas of biology Includes detailed coverage of the structure and regulation of all major matrix metalloproteinases Chapters focus on a timely and expanding field Topics have direct relevance to understanding human disease pathology of cancer, arthritis, and vascular disease Discusses latest strategies used in the development of new therapeutics to inhibit metalloproteinase activity

Discussing recent advances in the field of matrix metalloproteinase (MMP) research from a multidisciplinary perspective, Matrix Metalloproteinase Biologyis a collection of chapters written by leaders in the field of MMPs. The book focuses on the challenges of understanding the mechanisms substrate degradation by MMPs, as well as how these enzymes are able to degrade large, highly ordered substrates such as collagen. All topics addressed are considered in relation to disease progression including roles in cancer metastasis, rheumatoid arthritis and other inflammatory diseases. The text first provides an overview of MMPs, focusing on the history, the development and failures of small molecule inhibitors in clinical trials, and work with TIMPS, the endogenous inhibitors of MMPs. These introductory chapters establish the foundation for later discussion of the recent progress on the design of different types of inhibitors, including novel antibody based therapeutics. The following section emphasizes research using novel methods to further the study of the MMPs. The third and final section focuses on in vivo research, particularly with respect to cancer models, degradation of the extracellular matrix, and MMP involvement in other disease states. Written and edited by leaders in the field, Matrix Metalloproteinase Biology addresses the rapidly growth in MMP research, and will be an invaluable resource to advanced students and researchers studying cell and molecular biology.

Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.

Research in the matrix metalloproteinase field began with the demonstration by Gross and Lapière, in 1962, that resorbing tadpole tail expressed an enzyme that could degrade collagen gels. These humble beginnings have led us to the elucidation of around twenty distinct vertebrate MMPs, along with a variety of homologs from such diverse organisms as sea urchin, plants, nematode worm, and bacteria. This, coupled with four known specific inhibitors of MMPs, the TIMPs, gives a complex picture. Part I of Matrix Metalloproteinase Protocols provides the reader with a selective overview of the MMP arena, and a chance to come to grips with where the field has been, where it is, and where it is going. I hope that this complements all of the methodology that comes later. Part II presents the reader with a diverse set of methods for the expression and purification of MMPs and TIMPs, bringing together the long and often hard-earned experience of a number of researchers. Part III allows the reader to detect MMPs and TIMPs at both the protein and mRNA level, whereas Part IV gives the ability to assay MMP and TIMP activities in a wide variety of circumstances.

Matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes involved in physiological as well as in pathological processes in the human organism. MMPs play a key role in the remodeling of the extracellular matrix. Such a process may occur because of tissue homeostasis, morphogenesis, and tissue repair. However, remodeling could also be a part of many pathological states such as arthritis, cardiovascular diseases, neurodegenerative diseases, or impaired development in congenital anomalies. This book overviews the role of MMPs in different pathologies affecting the human body.