Expression and function of a receptor for hyaluronan-mediated motility on normal and malignant B lymphocytes.
Migration through extracellular matrix is fundamental to malignant invasion. A receptor for hyaluronan-mediated motility (RHAMM) has previously been shown to play a fundamental role in locomotion of ras-transformed cells as well as functioning in signal transduction. Expression of RHAMM was characterized on B lymphocytes from normal and malignant lymphoid tissues using multiparameter phenotypic immunofluorescence analysis as well as functional analysis of its role in locomotion of malignant hairy cell leukemia B cells. RHAMM is not detectable on most normal B cells located in blood, spleen, or lymph node, but it is detectable on bone marrow and thymic B cells. Among B-cell malignancies, it is expressed on most terminally differentiated B cells from multiple myeloma bone marrows, is present on a subset of non-Hodgkin's lymphomas, and is absent on B chronic lymphocytic leukemia. Activation of peripheral blood B cells by Staphylococcus A cowan (SAC), but not by pokeweed mitogen, induced transient expression of RHAMM at day 3 of culture, suggesting RHAMM may be used by antigen-activated normal B cells. For malignant cells, expression of RHAMM increased on long-term culture of bone marrow plasma cells from multiple myeloma patients, indicating prolonged expression in contrast to the transient expression on SAC-activated normal B cells. Intriguingly, RHAMM was expressed on hairy leukemia cells located in spleen but absent from those in peripheral blood of the same patient. RHAMM, as expressed on splenic hairy cells, was a 58-Kd molecule that binds hyaluronan, is encoded by a 5.2-kb messenger RNA, and participates in locomotion by these cells. Hairy cells locomoted in response to hyaluronan at 4 mu per minute. Monoclonal antibody to RHAMM inhibited this locomotion almost completely as detected using video time-lapse cinemicrography. These observations are consistent with a role for RHAMM in malignant invasion and metastatic growth.
Turley
E A
EA
Manitoba Institute for Cell Biology, University of Manitoba, Canada.
Belch
A J
AJ
Poppema
S
S
Pilarski
L M
LM
D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid / Q000494:pharmacology*; D015448:Leukemia, B-Cell / Q000276:immunology / Q000503:physiopathology*; D007943:Leukemia, Hairy Cell / Q000276:immunology / Q000503:physiopathology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000502:physiology; D008223:Lymphoma / Q000276:immunology / Q000503:physiopathology*; D009101:Multiple Myeloma / Q000276:immunology / Q000503:physiopathology*; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D006820:Hyaluronic Acid