Extracellular Matrix Degradation

Regulated turnover of extracellular matrix (ECM) is an important component of tissue homeostasis. In recent years, the enzymes that participate in, and control ECM turnover have been the focus of research that touches on development, tissue remodeling, inflammation and disease. This volume in the Biology of Extracellular Matrix series provides a review of the known classes of proteases that degrade ECM both outside and inside the cell. The specific EMC proteases that are discussed include cathepsins, bacterial collagenases, matrix metalloproteinases, meprins, serine proteases, and elastases. The volume also discusses the domains responsible for specific biochemical characteristics of the proteases and the physical interactions that occur when the protease interacts with substrate. The topics covered in this volume provide an important context for understanding the role that matrix-degrading proteases play in normal tissue remodeling and in diseases such as cancer and lung disease.

Regulated turnover of extracellular matrix (ECM) is an important component of tissue homeostasis. In recent years, the enzymes that participate in, and control ECM turnover have been the focus of research that touches on development, tissue remodeling, inflammation and disease. This volume in the Biology of Extracellular Matrix series provides a review of the known classes of proteases that degrade ECM both outside and inside the cell. The specific EMC proteases that are discussed include cathepsins, bacterial collagenases, matrix metalloproteinases, meprins, serine proteases, and elastases. The volume also discusses the domains responsible for specific biochemical characteristics of the proteases and the physical interactions that occur when the protease interacts with substrate. The topics covered in this volume provide an important context for understanding the role that matrix-degrading proteases play in normal tissue remodeling and in diseases such as cancer and lung disease.

Knowledge of the extracellular matrix (ECM) is essential to understand cellular differentiation, tissue development, and tissue remodeling. This volume of the series “Biology of Extracellular Matrix” provides a timely overview of the structure, regulation, and function of the major macromolecules that make up the extracellular matrix. It covers topics such as collagen types and assembly of collagen-containing suprastructures, basement membrane, fibronectin and other cell-adhesive glycoproteins, proteoglycans, microfibrils, elastin, fibulins and matricellular proteins, such as thrombospondin. It also explores the concept that ECM components together with their cell surface receptors can be viewed as intricate nano-devices that allow cells to physically organize their 3-D-environment. Further, the role of the ECM in human disease and pathogenesis is discussed as well as the use of model organisms in elucidating ECM function.

In most tissues, cells are surrounded by an extracellular matrix (ECM) containing proteins such as collagen, laminin, and fibronectin. The ECM plays an important role in regulating cell function. ECM proteins bind to integrins and other cell surface receptors, activating signaling pathways that regulate cellular morphology, adhesion, cell migration, cell proliferation, and apoptosis. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of ECM composition and function, as well as alterations in the ECM that occur during development, tumorigenesis, and other disease states. The contributors examine the various ECM proteins and proteoglycans, ECM receptors such as integrins, and the signaling pathways that mediate the effects of the ECM on cells. They also describe ECM functions in specific biological contexts, including angiogenesis, hemostasis, and thrombosis. Covering not only the biochemistry and cell biology of the ECM but also its roles in development, physiology, and pathology, this volume is an indispensable reference for cell biologists and all those interested in exploring the myriad functions of the ECM.

The extracellular matrix (ECM) is where cells live. It is composed of collagen and elastic fibers, glycosaminoglycans and proteoglycans, and several glycoproteins. In most tissues, fibril-forming collagen type I is the major constituent of ECM.The function of the ECM goes beyond providing mechanical support to cells and tissues. As cells are embedded into the ECM and interact with its components through their surface receptors, cell–ECM interaction plays a key role in influencing different cell activities, such as cell proliferation and migration. The ECM also sequesters and releases growth factors affecting important cellular pathways. Overall, the ECM strongly influences and affects cell behavior and tissue homeostasis. ECM is a highly dynamic structural network that continuously undergoes controlled remodeling mediated by matrix-degrading enzymes, the matrix metalloproteinases (MMPs), under normal conditions. Quantitative and qualitative deregulation of ECM remodeling and, especially, of collagen turnover, is responsible for the alteration of ECM composition and structure, associated with the development and progression of several pathological conditions, such as organ fibrosis (determined by the abnormal accumulation of ECM components) and tumor invasion. The understanding of the diverse biological roles and properties of the ECM components is pivotal to the development of new therapeutic tools for disease treatment.

In the ten-year interval since the first edition of this volume went to press, our knowledge of extracellular matrix (ECM) function and structure has enor mously increased. Extracellular matrix and cell-matrix interaction are now routine topics in the meetings and annual reviews sponsored by cell biology societies. Research in molecular biology has so advanced the number of known matrix molecules and the topic of gene structure and regulation that we won dered how best to incorporate the new material. For example, we deliberated over the inclusion of chapters on molecular genetics. We decided that with judicious editing we could present the recent findings in molecular biology within the same cell biology framework that was used for the first edition, using three broad headings: what is extracellular matrix, how is it made, and what does it do for cells? Maintaining control over the review of literature on the subject of ECM was not always an easy task, but we felt it was essential to production of a highly readable volume, one compact enough to serve the the student as an introduction and the investigator as a quick update on graduate the important recent discoveries. The first edition of this volume enjoyed con hope the reader finds this edition equally useful. siderable success; we D. Hay Elizabeth vii Contents Introductory Remarks 1 Elizabeth D. Hay PART I. WHAT IS EXTRACELLULAR MATRIX? Chapter 1 Collagen T. F. Linsenmayer 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2. The Collagen Molecule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2. 1. Triple-Helical Domain(s) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Looking at the area of the extracellular matrix of connective tissue, including the results and concepts which have recently been generated, this text describes the structural characteristics of extracellular molecules and discusses the interaction between the cell and the extracellular matrix.