HYALURONAN-DEPENDENT MOTILITY OF B-CELLS AND LEUKEMIC PLASMA-CELLS INBLOOD, BUT NOT OF BONE-MARROW PLASMA-CELLS, IN MULTIPLE-MYELOMA - ALTERNATE USE OF RECEPTOR FOR HYALURONAN-MEDIATED MOTILITY (RHAMM) AND CD44

We investigated the ability of blood B cells, bone marrow (BM) plasma cells, and terminal leukemic plasma cells (T-PCL) from patients with m ultiple myeloma (MM) to migrate on extracellular matrix proteins. Hyal uronan (HA), but not collagen type I, collagen type IV, or laminin, pr omoted migration of MM blood B cells, as determined by time-lapse vide o microscopy. Between 13% and 20% of MM blood B cells migrated on HA w ith an average velocity of 19 mu m/min, and greater than 75% of MM blo od B cells exhibited vigorous cell movement and plasma membrane deform ation, as did circulating T-PCL and extraskeletal plasma cells from pa tients 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 an d MM plasma cells from all sources examined expressed the HA-binding r eceptors receptor for HA-mediated motility (RHAMM) and CD44. On circul ating MM B cells, both RHAMM and CD44 participated in HA-binding, indi cating their expression ex vivo in an activated conformation. In contr ast, for the majority of BM plasma cells in the majority of patients w ith 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 RH AMM and CD44, migration of MM blood B cells on HA was inhibited by ant i-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 e xhibit RHAMM- and HA-dependent motile behavior indicative of migratory potential, while BM plasma cells are sessile. We speculate that a sub set(s) of circulating B or plasma cells mediates malignant spread in m yeloma. (C) 1996 by The American Society of Hematology.