Role of extracellular matrix in pancreatic diseases.

Accessible online at: http://BioMedNet.com/karger The extracellular matrix (ECM) has been traditionally thought of as the structurally stable material that provides support for cells and tissues. However, a number of discoveries over the past decades have changed this view. First, it has been shown that four major classes of macromolecules – the collagens, proteoglycans, structural glycoproteins, and elastin – collectively comprise the ECM of animal cells [1–6]. Furthermore, with the exception of elastin, each class of matrix macromolecules has been found to contain families of related proteins with each member being a unique gene product. Second, individual members of each class and family of ECM molecules were found to exhibit a degree of tissue-specific distribution implicating the matrix in development and tissue function [7, 8]. Third, specific cell-surface receptors for ECM components were identified, which provided a rational basis for linking the ECM with the cell [9–11]. From these discoveries it is now evident that the extracellular matrix is composed of a number of different macromolecules whose structural integrity and functional composition are important in maintaining normal tissue architecture, in development and in tissue-specific function [2, 4, 6, 8, 12]. Finally, it has been recognized that dysfunctional matrix components and abnormalities in ECM biosynthesis and catabolism are of importance in both inherited and acquired diseases and in normal wound healing [2, 3, 5, 6]. In particular pancreatic diseases as, e.g., pancreatic cancer and chronic pancreatitis are characterized by profound alterations of ECM formation and composition. The following review summarizes some of the major aspects that have emerged in the recent years concerning composition, formation and regulation of the ECM in human pancreatic diseases and in experimental models of pancreatic fibrosis.