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

• Published in: Blood Vol. 87; no. 5; pp. 1891 - 1899
• Main Authors: Masellis-Smith, A., Belch, A.R., Mant, M.J., Turley, E.A., Pilarski, L.M.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.03.1996; The Americain Society of Hematology
• Subjects: B-Lymphocyte Subsets - drug effects; B-Lymphocyte Subsets - ultrastructure; Biological and medical sciences; Bone Marrow - pathology; Cell Adhesion; Cell Membrane - ultrastructure; Chemotaxis, Leukocyte - drug effects; Extracellular Matrix Proteins - drug effects; Extracellular Matrix Proteins - physiology; Hematologic and hematopoietic diseases; Humans; Hyaluronan Receptors - drug effects; Hyaluronan Receptors - physiology; Hyaluronic Acid - pharmacology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Microscopy, Electron, Scanning; Multiple Myeloma - pathology; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - ultrastructure; Plasma Cells - classification; Plasma Cells - drug effects; Protein Binding; Human; Immunopathology; Mobility; Malignant hemopathy; B-Lymphocyte; Plasmocyte; Myeloma; Biological fixation; Regulation(control); Immunoglobulinopathy; Ex vivo; Lymphoproliferative syndrome; Bone marrow; Developmental stage; Tumor cell; Biological receptor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V87.5.1891.1891

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 μm/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.