Binding of a large chondroitin sulfate/dermatan sulfate proteoglycan, versican, to L-selectin, P-selectin, and CD44

Here:we show that a large chondroitin sulfate proteoglycan, versican, deriv ed from a renal adenocarcinoma cell line ACHN, binds L-selectin, P-selectin , and CD44. The binding was mediated by the interaction of the chondroitin: sulfate (CS) chain of versican with the carbohydrate-binding domain of L- a nd P-selectin and CD44. The binding of versican to L- and P-selectin was in hibited by CS B, CS E, and heparan sulfate (HS) but not by: any other glyco saminoglycans tested. On the other hand, the binding to CD44 was inhibited by hyaluronic acid, chondroitin (CH), CS A, CS B, CS C, CS D, and CS E but not by HS or keratan sulfate. A cross-blocking study indicated that L- and P-selectin recognize: close or overlapping sites on versican, whereas CD44 recognizes separate sites. We also show that soluble L- and P-selectin dire ctly bind to immobilized CS B, CS E, and HS and that soluble CD44 directly binds to immobilized hyaluronic acid, CH, and all the CS chains examined. C onsistent with these results, structural analysis showed that versican is m odified with at least CS B and CB C. Thus, proteoglycans sufficiently modif ied with the appropriate glycosaminoglycans should be able: to bind L-selec tin, P-selectin, and/or CD44.