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-extracellular matrix adhesion. In this study, we examined myeloma cell lines for cell membrane localization of syndecan-1. On some cells we note a striking localization of syndecan-1 to a single small membrane protrusion, with the remainder of the cell surface being mostly negative for syndecan-1. Examination of cell morphology reveals that a proportion of cells from myeloma cell lines, as well as primary myeloma cells, are polarized, with a uropod on one end and lamellipodia on the other end. On these polarized cells, syndecan-1 is specifically targeted to the uropod, but in contrast, on nonpolarized cells syndecan-1 is evenly distributed over the entire cell surface. In addition to syndecan-1, several other cell surface molecules localize specifically to the uropod, including CD44 and CD54. Functional assays reveal that myeloma cell lines with a high proportion of polarized cells have a much higher migratory potential than cell lines with few polarized cells. Moreover, the uropod is the cell pole preferentially involved in aggregation of myeloma cells and in adhesion of myeloma cells to osteoblast-like cells. When polarized myeloma cells are incubated with heparin-binding proteins, like hepatocyte growth factor or osteoprotegerin, they concentrate in the uropod. These data indicate that syndecan-1 is targeted to the uropod of polarized myeloma cells and that this targeting plays a role in promoting cell-cell adhesion and may also regulate the biological activity of heparin-binding cytokines.
Børset
M
M
Arkansas Cancer Research Center and Departments of Pathology and Anatomy, University of Arkansas for Medical Sciences, Little Rock, AR, USA. magne.borset@medixin.ntnu.no
Hjertner
O
O
Yaccoby
S
S
Epstein
J
J
Sanderson
R D
RD
D000818:Animals; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D002465:Cell Movement; D016764:Cell Polarity; D004847:Epithelial Cells / Q000648:ultrastructure; D006023:Glycoproteins / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D026563:LDL-Receptor Related Protein-Associated Protein; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000502:physiology; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000473:pathology*; D053244:Osteoprotegerin; D011509:Proteoglycans / Q000032:analysis* / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D053668:Syndecan-1; D053667:Syndecans; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D026563:LDL-Receptor Related Protein-Associated Protein; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D011509:Proteoglycans; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse; D018799:Intercellular Adhesion Molecule-1; D017228:Hepatocyte Growth Factor