HEPARAN SULFATE-MEDIATED CELL-AGGREGATION - SYNDECAN-1 AND SYNDECAN-4MEDIATE 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 ad hesion. However, there has been no direct evidence to support this not ion. To address this question, B lymphoid (ARH-77) cells were transfec ted with the cDNA for murine syndecan-1. Unlike the parental cells, th e transfectants form large multicellular aggregates in suspension cult ures 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 i s inhibited by the following: (i) addition of heparin and heparin-like glycosaminoglycans, (ii) removal of heparan sulfate from the cell sur face, or (iii) addition of exogenous purified syndecan-1. Mixing of sy ndecan-1-transfected and control-transfected cells results in aggregat es containing both cell types indicating that aggregation occurs throu gh a heterophilic adhesion mechanism in which heparan sulfate chains b ind to a counter-receptor present on these cells. Importantly, syndeca n 4-transfected cells also aggregate in a heparan sulfate dependent ma nner, while in contrast, betaglycan-transfected cells aggregate poorly , Thus, syndecans may be important mediators of cell-cell adhesion, bu t this function may not be common to all transmembrane heparan sulfate -bearing proteoglycans.