Chapter 12 - Regulation of cell behavior by extracellular proteins

Abstract

The extracellular milieu is a critical determinant of cell behavior in all tissues. Many factors comprise the environment and each factor contributes to cell behavior. For example, cell:cell contact, cell:extracellular matrix (ECM) interaction, and ECM composition influence cell activity. Environmental components act together to regulate cell surface protein activity, intracellular signal transduction, and subsequent gene expression, which leads to proliferation, migration, differentiation, and ultimately the formation of complex tissues. Matricellular proteins secreted, modular proteins that are associated with the ECM, are known to influence cell adhesion, cell:ECM binding, and ECM structure and function. This chapter will focus on matricellular proteins as modulators of extracellular signals. A unifying theme of matricellular proteins is to provide a link between the ECM and cell surface receptors, and/or cytokines and proteases localized in the extracellular environment, the activity of which might be affected by this interaction. Thrombospondins-1 and -2, tenascin-C, osteopontin, and secreted protein acidic and rich in cysteine are representatives of this class of proteins. A growing body of evidence points to these proteins as important mediators of cell signaling pathways and ECM assembly and turnover. Consequently, strategies designed to recapitulate tissue environments should consider the influence of matricellular proteins.