gms | German Medical Science

Cell proliferation and growth not only requires interaction between cellular receptors and growth factors, but is also linked to interactions of cells with their microenvironment. Therefore, the extracellular matrix (ECM) surrounding the cells is just as important for growth regulation as the interaction between soluble growth-regulating molecules and their cellular receptors. The extracellular matrix is formed by a complex of self-assembling macromolecules, composed predominantly of collagens, non-collagenous glycoproteins, elastin, hyaluronan and proteoglycans. Besides being a scaffold for the cells, the extracellular matrix serves as a reservoir for growth factors and cytokines and influences their activation status and turnover. As growth factors interact with extracellular matrix molecules, they may become sequestered from their signalling receptors, become activated, e.g., by proteolytic processing, and they may be presented to the cells in a specific manner which alters their biological function. Beyond this, recent investigations show that extracellular matrix proteins may exert a direct signalling function, either by means of interactions with matrix receptors such as integrins or via direct interaction with growth factor receptors. This network of interactions has recently been investigated in detail for the group of extracellular matrix proteoglycans, and raises the discussion of ECM to a novel level of complexity. Excessive production of extracellular fibrotic tissue is a hallmark of pancreatic cancer. Although pancreatic cancer cells are capable of producing main ECM components such as collagen I, III, IV, fibronectin, and others, pancreatic myofibroblasts / stellate cells are the main producers of this newly formed tissue. Numerous studies have provided strong evidence that these cells play a central role in fibrogenesis in pancreatic cancer. In recent years, discussion has focused on analysis of specific signal transduction pathways and mechanisms for regulating the activity of pancreatic stellate cells. In pancreatic cancer the significance of the excessive production of the ECM remains to be clarified. Thus far it is not known whether the newly formed stroma favours tumour growth or represents a host reaction designed to confine the invading cancer.