Matricellular proteins are secreted into the extracellular environment, or matrix, but do not play a primary structural role in this location. Rather, these proteins modulate cell function by interacting with cell-surface receptors, proteases, hormones, and other bioeffector molecules, as well as with structural matrix proteins such as collagens. The term ‘matricellular’was introduced to explain the unusual diversity of functions that were beginning to be recognized in proteins such as thrombospondin-1 (TSP-1), SPARC, and tenascin-C.(Sage and Bornstein 1991; Bornstein 1995). The intent of segregating this subclass of secreted proteins was to emphasize that the extracellular environment was a major factor in regulating their synthesis, a process that had been termed ‘dynamic reciprocity’at an earlier date (Bornstein et al. 1982). A review that summarized many of the considerations that led to the concept of matricellular proteins was published in Methods in Cell Biology (Bornstein 2002).

In additional reviews (Bornstein 2001; Bornstein and Sage 2002) some of the distinguishing characteristics of matricellular proteins were summarized in greater detail. These included: 1) high levels of expression during development and in response to injury; 2) binding to many cell-surface receptors, components of the extracellular matrix, growth factors, cytokines, and proteases; 3) induction of de-adhesion or counter-adhesion in contrast to the adhesivity of most matrix proteins (Murphy-Ullrich 2001; Liu et al. 2009), and 4) a grossly normal or subtle phenotype that is observed in mice with a targeted disruption