Heparan sulfate-mediated cell aggregation. Syndecans-1 and -4 mediate intercellular adhesion following their transfection into human B lymphoid cells.
Because syndecans are present at sites of cell-cell contact in vivo it has been hypothesized that they play a role in mediating cell-cell adhesion. However, there has been no direct evidence to support this notion. To address this question, B lymphoid (ARH-77) cells were transfected with the cDNA for murine syndecan-1. Unlike the parental cells, the transfectants form large multicellular aggregates in suspension cultures and stain intensely for syndecan-1 at sites of cell-cell contact. Using rotation-mediated aggregation assays, we find that aggregation of syndecan-1-transfected cells is dependent on divalent cations and is inhibited by the following: (i) addition of heparin and heparin-like glycosaminoglycans, (ii) removal of heparan sulfate from the cell surface, or (iii) addition of exogenous purified syndecan-1. Mixing of syndecan-1-transfected and control-transfected cells results in aggregates containing both cell types indicating that aggregation occurs through a heterophilic adhesion mechanism in which heparan sulfate chains bind to a counter-receptor present on these cells. Importantly, syndecan-4-transfected cells also aggregate in a heparan sulfate-dependent manner, while in contrast, betaglycan-transfected cells aggregate poorly. Thus, syndecans may be important mediators of cell-cell adhesion, but this function may not be common to all transmembrane heparan sulfate-bearing proteoglycans.
Stanley
M J
MJ
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock 72205.
Liebersbach
B F
BF
Liu
W
W
Anhalt
D J
DJ
Sanderson
R D
RD
D000818:Animals; D001402:B-Lymphocytes; D002413:Cations, Divalent / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D011509:Proteoglycans / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D053668:Syndecan-1; D053671:Syndecan-4; D053667:Syndecans; D014162:Transfection
D002413:Cations, Divalent; D002809:Chondroitin Sulfates; D004492:Edetic Acid; D006493:Heparin; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D053668:Syndecan-1; D053671:Syndecan-4; D053667:Syndecans; C508241:SDC1 protein, human; C508304:SDC4 protein, human; C508242:Sdc1 protein, mouse; C508306:Sdc4 protein, mouse