Blood, 1 October 2000, Vol. 96, No. 7, pp. 2528-2536
NEOPLASIA
Syndecan-1 is targeted to the uropods of polarized myeloma cells
where it promotes adhesion and sequesters heparin-binding
proteins
Magne Børset,
Øyvind Hjertner,
Shmuel Yaccoby,
Joshua Epstein, and
Ralph D. Sanderson
From Arkansas Cancer Research Center and Departments of
Pathology and Anatomy, University of Arkansas for Medical Sciences,
Little Rock, AR; and Institute of Cancer Research and Molecular
Biology, Norwegian University of Science and Technology, Trondheim,
Norway.
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.
