Regulation of cell-substrate adhesion by proteoglycans immobilized on extracellular substrates.
We have demonstrated previously that chick embryo fibroblasts synthesize and secrete a large chondroitin sulfate proteoglycan (designated PG-M) that binds to fibronectin. We now report the possibility that PG-M interactions with cell surfaces can modulate cell-substrate adhesion. When PG-M was added to the medium, various types of trypsinized cells failed to adhere not only to fibronectin-coated substrates but also to collagen- or vitronectin-coated substrates. Adhesion of the cells to laminin or glycyl-arginyl-glycyl-aspartyl-serine derivatized serum albumin (arginyl-glycyl-aspartic acid-containing molecules with no capacity to bind PG-M) was also inhibited by PG-M. Treatment of the proteoglycan with either proteolytic enzymes or chondroitinase abolished its inhibitory effects on the cell adhesion. These results suggest that direct binding between PG-M and fibronectin, if any, is not a cause of the inhibition by PG-M and that only the proteoglycan form is responsible for the activity. When the immobilization of added PG-M to available plastic surfaces of coated dishes was blocked by pretreating the dishes with serum albumin, the inhibitory effect of PG-M was abolished, suggesting that the immobilized fraction of PG-M can act as a cell adhesion inhibitor. In immobilized form, both cartilage chondroitin sulfate proteoglycan (designated PG-H) and chondroitin sulfate-derivatized serum albumin also inhibited cell adhesion. In contrast, heparan sulfate proteoglycan form LD and heparan sulfate-derivatized serum albumin had far lower inhibitory activities, indicating that the active site for the interaction between cells and PG-M is on the chondroitin sulfate chains.
Yamagata
M
M
Institute for Molecular Science of Medicine, Aichi Medical University, Japan.
Suzuki
S
S
Akiyama
S K
SK
Yamada
K M
KM
Kimata
K
K
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D002642:Chick Embryo; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D007797:Laminin / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology*; D051381:Rats; D012709:Serum Albumin / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology; D019096:Vitronectin
D011508:Chondroitin Sulfate Proteoglycans; D003094:Collagen; D005353:Fibronectins; D006023:Glycoproteins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007797:Laminin; D009842:Oligopeptides; D011509:Proteoglycans; D012709:Serum Albumin; D014357:Trypsin; D019096:Vitronectin; C049554:glycyl-arginyl-glycyl-aspartyl-serine