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Hairy cell interactions with extracellular matrix: expression of specific
integrin receptors and their role in the cell's response to specific
adhesive proteins
J Burthem, PK Baker, JA Hunt and JC Cawley
Department of Haematology, University of Liverpool, UK.
Integrin/extracellular-matrix interactions are central to the migration,
localization, and subsequent function of lymphocytes within tissues. In
hairy cell leukemia (HCL) the malignant cells display a highly
characteristic tissue distribution in which interactions with extracellular
matrix (ECM) are often prominent. Therefore, we used HCL as a model in
which to investigate the poorly understood integrin/ECM interactions that
underlie the migratory behavior of malignant B lymphocytes. Using a
combined approach involving immunocytochemistry, flow cytometry, and
immunoprecipitation analysis, hairy cells (HCs) were shown to have a
consistent and distinctive phenotype (mainly alpha 4 beta 1, alpha 5 beta
1, alpha v beta 1, and alpha v beta 3). Furthermore, functional studies
utilising adhesion assays, time-lapse video-microscopy and image analysis
showed that the HCs displayed very specific adhesive behaviour in response
to relevant adhesive protein ligands. HCs were able to adhere to different
extents on all the adhesive proteins examined, but, on laminin and
collagen, binding was weak with little cytoplasmic spreading. In contrast,
the cells showed strong adhesion both to fibronectin (FN) and to
vitronectin (VN). On FN, the cells spread extensively with nonpolarized
cytoplasmic projections, whereas on VN cytoplasmic projections were
markedly polarized. This polarized morphology was shown to reflect cell
motility. Investigation of the role of individual integrin receptors in the
cell movement response suggested that alpha v beta 3 is the major integrin
responsible for this motile behavior. These results are discussed in
relation to the limited previous data on leukemic and activated B-cell
integrins, and we suggest that the HC integrins play a significant role in
the characteristic behavior of HCs within tissues.
Volume 84,
Issue 3,
pp. 873-882,
08/01/1994
Copyright © 1994 by The American Society of Hematology
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