EPICAN, A HEPARAN CHONDROITIN SULFATE PROTEOGLYCAN FORM OF CD44, MEDIATES CELL-CELL ADHESION

Epican is a heparan/chondroitin sulfate proteoglycan form of CD44 and is expressed on the surface of keratinocytes from the basal layer to t he granular layer of the epidermis. To analyze the adhesive properties of epican apart from the influence of other adhesive molecules found on keratinocytes, mouse L cell fibroblasts were transfected with CD44E pican cDNA. The epican expressed on the surface of transfected L cells was predominantly a heparan or chondroitin sulfate proteoglycan. The CD44Epican-transfected L cells acquired: (a) a self-aggregating phenot ype that required hyaluronan but was calcium-independent; and (b) a ne w capacity to adhere to keratinocytes, a property that was blocked by an anti-epican antibody. Both aggregation and adhesion of CD44Epican-t ransfected cells were completely prevented by pretreatment with hyalur onidase, but were totally restored by the addition of exogenous hyalur onan, Aggregation of transfected L cells was minimally influenced by o ther glycosaminoglycans, but adhesion of transfected L cells to kerati nocytes was substantially inhibited by heparin. The ability of epican to mediate adhesion between keratinocytes was evaluated in a newly dev eloped adhesion assay, In the presence of 0.03 mM calcium, a monoclona l antibody against epican inhibited keratinocyte adhesion to keratinoc yte monolayers by 80%. These data demonstrate that epican causes adhes ion and aggregation in the transfected L cell model system, that the a dhesive function of epican is hyaluronan-dependent, and that epican co uld have an adhesive function in intact epidermis.