Syndecan-1 is targeted to the uropods of polarized myeloma cells where it promotes adhesion and sequesters heparin-binding proteins

Syndecan-1 (CD138) is a heparan sulfate-bearing proteoglycan present on the surface of myeloma cells where it mediates myeloma cell-cell and cell-extr acellular matrix adhesion. In this study, we examined myeloma cell lines fo r cell membrane localization of syndecan-1. On some cells we note a strikin g localization of syndecan-1 to a single small membrane protrusion, with th e remainder of the cell surface being mostly negative for syndecan-1. Exami nation of cell morphology reveals that a proportion of cells from myeloma c ell lines, as well as primary myeloma cells, are polarized, with a uropod o n one end and lamellipodia on the other end. On these polarized cells, synd ecan-1 is specifically targeted to the uropod, but in contrast, on nonpolar ized cells syndecan-1 is evenly distributed over the entire cell surface. I n addition to syndecan-1, several other cell surface molecules localize spe cifically to the uropod, including CD44 and CD54, Functional assays reveal that myeloma cell lines with a high proportion of polarized cells have a mu ch higher migratory potential than cell lines with few polarized cells. Mor eover, the uropod is the cell pole preferentially involved in aggregation o f myeloma cells and in adhesion of myeloma cells to osteoblast-like cells. When polarized myeloma cells are incubated with heparin-binding proteins, l ike hepatocyte growth factor or osteoprotegerin, they concentrate in the ur opod. These data indicate that syndecan-1 is targeted to the uropod of pola rized myeloma cells and that this targeting plays a role in promoting cell- cell adhesion and may also regulate the biological activity of heparin-bind ing cytokines, (Blood, 2000;96: 2528-2536) (C) 2000 by The American Society of Hematology.