HEPARAN-SULFATE PROTEOGLYCANS AS ADHESIVE AND ANTI-INVASIVE MOLECULES- SYNDECANS AND GLYPICAN HAVE DISTINCT FUNCTIONS

ARH-77 cells do not adhere to type I collagen and readily invade into collagen gels, but following expression of the transmembrane heparan s ulfate proteoglycan syndecan-1, they bind collagen and fail to invade. We now show that cells transfected with syndecan-2 or syndecan-4 also bind collagen and are non-invasive. In contrast, cells transfected wi th the glycosylphosphatidylinositol-anchored proteoglycan glypican-1 d o not bind to collagen and remain invasive, even though glypican- and syndecan-expressing cells have similar surface levels of heparan sulfa te, and their proteoglycans have similar affinities for collagen. Anal ysis of cells expressing syndecan-1-glypican-1 chimeric proteoglycans reveals that inhibition of invasion requires the extracellular domain of syndecan but not its transmembrane or cytoplasmic domain. Surprisin gly, cells bearing a chimera composed of the glypican extracellular do main fused to the syndecan transmembrane and cytoplasmic domains bind to collagen but remain invasive, implying that adhesion to collagen is not by itself sufficient to inhibit invasion. Apparently, the extrace llular domain of syndecan-1, presumably by interacting with cell-surfa ce signal transducing molecules, directly regulates complex cell behav iors such as motility and invasiveness. These results also show for th e first time that syndecans and glypicans can have distinct functions, even when expressed by the same cell type.