Regulation of cell substrate adhesion: effects of small galactosaminoglycan-containing proteoglycans.

Abstract

Cell adhesion is a process which is initiated by the attachment of cells to specific sites in adhesive matrix proteins via cell surface receptors of the integrin family. This is followed by a reorganization of cytoskeletal elements which results in cell spreading and the formation of focal adhesion plaques. We have examined the effects of a class of small galactosaminoglycan-containing proteoglycans on the various stages of cell adhesion to fibronectin-coated substrates. Our results indicate that dermatan sulfate proteoglycans (DSPGs) derived from cartilage, as well as other related small proteoglycans, inhibit the initial attachment of CHO cells and rat embryo fibroblasts to substrates composed of the 105-kD cell-binding fibronectin fragment, but do not affect cell attachment to intact fibronectin. Although this effect involves binding of DSPGs to the substrate via the protein core, the intact proteoglycan is necessary for the observed activity. Isolated core proteins are inactive. The structural composition of the galactosaminoglycan chain does not appear to be functionally significant since both chondroitin sulfate and various dermatan sulfate proteoglycans of this family inhibit cell attachment to the fibronectin fragment. Neither the percentage of cells spread nor the mean area of spread cells adhering to substrates of intact fibronectin was significantly affected by the DSPGs. However, significantly fewer cells formed focal adhesions in the presence of DSPGs as compared with untreated control cells. These results suggest that the binding of small galactosaminoglycan-containing proteoglycans to a fibronectin substrate may affect several stages in the cell adhesion process.

Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness

“…Adhesion of a cell to its ECM starts with the recognition of particular domains in adhesive proteins of the matrix, such as laminin, fibrinogen, fibronectin, vitronectin, and some collagens, by structurally relatedplasma membrane receptors, called integrins. After this initial cell-substrate attachment, cytoskeletal elements reorganize and cause cell spreading and flattening and subsequently, focal adhesion formation (Bidanset et al 1992).…”

Decorin suppresses tumor cell-mediated angiogenesis

“…It has been previously shown that decorin interacts with fibronectin and laminin, and that it functions as an antiadhesive molecule (Schmidt et al, 1987;Bidanset et al, 1992). To this end, we performed experiments in which HUVECs were first primed for 18 h with either serumfree medium (SFM) or media conditioned by each tumor cell type, then detached and assayed them for their ability to adhere to laminin-coated (0 -5 mg) wells.…”

The binding capacity of α1β1-, α2β1- and α10β1-integrins depends on non-collagenous surface macromolecules rather than the collagens in cartilage fibrils

“…In agreement with this notion, we presented evidence here that the mostly non-collagenous components of collagen-containing fibrils in cartilage contain the relevant binding sites for integrins. Molecular candidates include collagen VI and microfibrils containing collagen VI [24], matrilins [11], COMP (thrombospondin 5) [13], and several SLRPs (decorin, fibromodulin, lumican) [44]. Many of these macromolecules have been associated also with a biomechanical role in cartilage (for review see [12]).…”