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Expression and function of a receptor for hyaluronan-mediated motility on
normal and malignant B lymphocytes
EA Turley, AJ Belch, S Poppema and LM Pilarski
Manitoba Institute for Cell Biology, University of Manitoba, Canada.
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.
Volume 81,
Issue 2,
pp. 446-453,
01/15/1993
Copyright © 1993 by The American Society of Hematology
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