SPARC, a matricellular protein: at the crossroads of cell-matrix

SPARC is a multifunctional glycoprotein that belongs to the matricellular g roup of proteins. It modulates cellular interaction with the extracellular matrix (ECM) by its binding to structural matrix proteins, such as collagen and vitronectin, and by its abrogation of focal adhesions, features contri buting to a counteradhesive effect on cells. SPARC inhibits cellular prolif eration by an arrest of cells in the G1 phase of the cell cycle. It also re gulates the activity of growth factors, such as platelet-derived growth fac tor (PDGF), fibroblast growth factor (FGF)-2, and vascular endothelial grow th factor (VEGF). The expression of SPARC in adult animals is limited large ly to remodeling tissue, such as bone, gut mucosa, and healing wounds, and it is prominent in tumors and in disorders associated with fibrosis. The cr ystal structure of two of the three domains of the protein has revealed a n ovel follistatin-like module and an extracellular calcium-binding (EC) modu le containing two EF-hand motifs. The follistatin-like module and the EC mo dule are shared by at least four other proteins that comprise a family of S PARC-related genes. Targeted disruption of the SPARC locus in mice has show n that SPARC is important for lens transparency, as SPARC-null mice develop cataracts shortly after birth. SPARC is a prototypical matricellular prote in that functions to regulate cell-matrix interactions and thereby influenc es many important physiological and pathological processes. (C) Elsevier Sc ience B.V./International Society of Matrix Biology. All rights reserved.