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Hyaluronan-dependent motility of B cells and leukemic plasma cells in
blood, but not of bone marrow plasma cells, in multiple myeloma: alternate
use of receptor for hyaluronan-mediated motility (RHAMM) and CD44
A Masellis-Smith, AR Belch, MJ Mant, EA Turley and LM Pilarski
Department of Oncology, University of Alberta, Edmonton, Canada.
We investigated the ability of blood B cells, bone marrow (BM) plasma
cells, and terminal leukemic plasma cells (T-PCL) from patients with
multiple myeloma (MM) to migrate on extracellular matrix proteins.
Hyaluronan (HA), but not collagen type I, collagen type IV, or laminin,
promoted migration of MM blood B cells, as determined by time-lapse video
microscopy. Between 13% and 20% of MM blood B cells migrated on HA with an
average velocity of 19 micron/min, and greater than 75% of MM blood B cells
exhibited vigorous cell movement and plasma membrane deformation, as did
circulating T-PCL and extraskeletal plasma cells from patients with MM. In
contrast, plasma cells obtained from BM of patients with MM lacked motility
on all substrates tested and did not exhibit cell membrane protrusions or
cellular deformation. MM blood B cells and MM plasma cells from all sources
examined expressed the HA- binding receptors receptor for HA-mediated
motility (RHAMM) and CD44. On circulating MM B cells, both RHAMM and CD44
participated in HA- binding, indicating their expression ex vivo in an
activated conformation. In contrast, for the majority of BM plasma cells in
the majority of patients with MM, expression of RHAMM or CD44 was not
accompanied by HA binding. A minority of patients did have HA-binding BM
plasma cells, involving both RHAMM and CD44, as evidenced by partial
blocking with monoclonal antibodies (MoAbs) to RHAMM or to CD44. Despite HA
binding by both RHAMM and CD44, migration of MM blood B cells on HA was
inhibited by anti-RHAMM but not by anti-CD44 MoAbs, indicating that RHAMM
but not CD44 mediates motility on HA. Thus, circulating B and plasma cells
in MM exhibit RHAMM- and HA-dependent motile behavior indicative of
migratory potential, while BM plasma cells are sessile. We speculate that a
subset(s) of circulating B or plasma cells mediates malignant spread in
myeloma.
Volume 87,
Issue 5,
pp. 1891-1899,
03/01/1996
Copyright © 1996 by The American Society of Hematology
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