[CITATION][C] Extracellular proteins that modulate cell-matrix interactions. SPARC, tenascin, and thrombospondin

EH Sage, P Bornstein - Journal of Biological Chemistry, 1991 - Elsevier
EH Sage, P Bornstein
Journal of Biological Chemistry, 1991Elsevier
It is almost axiomatic in cell biology to accept the postulate that cells normally adherent in
uiuo require attachment and spreading in uitro to proliferate and to express their
differentiated properties. Experimental verification of this hypothesis focused attention on the
nature of adhesive macromolecules in the extracellular matrix (ECM)'and the characteristics
and consequences of their interactions with cell-surface receptors (1-8). The major adhesive
macromolecules for epithelial and mesenchymal cells include fibronectin (FN), vitronectin …
It is almost axiomatic in cell biology to accept the postulate that cells normally adherent in uiuo require attachment and spreading in uitro to proliferate and to express their differentiated properties. Experimental verification of this hypothesis focused attention on the nature of adhesive macromolecules in the extracellular matrix (ECM)’and the characteristics and consequences of their interactions with cell-surface receptors (1-8). The major adhesive macromolecules for epithelial and mesenchymal cells include fibronectin (FN), vitronectin, laminin, entactin, the fibrillar collagens (types I, 11, 111, V, and XI), and the collagen in basement membranes (type IV); these components interact with a variety of integrins, heparan sulfate proteoglycans, and other cell-surface receptors. However, it is apparent that the interaction of a cell with its environment must be a dynamic one, since cells that ordinarily remain attached in uiuo must also be capable of diminishing adhesive forces for rounding and division. In addition, it seems probable that, for many cells, differentiation requires a number of cell divisions, and cell movement requires the making and breaking of interactions with an ECM. We describe in this review a group of secreted glycoproteins that presently includes SPARC, tenascin (TN), and thrombospondin (TSP) but that is likely to include other macromolecules with related functions. These proteins do not function primarily and generally as cell adhesion factors, in the sense that they foster both attachment and spreading in most cells. Instead, for many cells, these proteins exert an “anti-adhesive” function that leads to cell rounding and partial detachment from a substratum. SPARC, TN, and TSP possess certain common attributes. Although these proteins are secreted and retained in the local environment where they can function in an autocrine and paracrine fashion, they do not usually accumulate or function as structural components in the normal adult organism. SPARC, TN, and TSP appear to play dynamic roles in embryogenesis and morphogenesis. I n uitro, there is a positive association between synthesis and cell proliferation, and all three proteins have been shown to promote changes in cell shape, with attendant consequences for cell behavior.
Cells that produce an ECM are also influenced by it, a concept that we and others have termed “dynamic reciprocity.” Since there are no major structural similarities among SPARC, TN, and TSP, it is likely that these proteins exert their proximal effects, ie an interference with focal adhesions leading to changes in cell shape (9-12), by different mechanisms. Possibilities include activation of intracellular signaling pathways (13), occlusion or interference with cell attachment to proteins like FN (3, 14, 151, an influence on Ca’+ ion flux, presentation or monopolization of growth factors and cytokines (16, 17), and modulation
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