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Blood, 1 November 2000, Vol. 96, No. 9, pp. 3161-3167
NEOPLASIA
Involvement of CD44-hyaluronan interaction in malignant cell
homing and fibronectin synthesis in hairy cell leukemia
Khalil A. Aziz,
Kathleen J. Till,
Mirko Zuzel, and
John C. Cawley
From the Department of Haematology, University of
Liverpool, Liverpool, United Kingdom.
The tissue homing of malignant hematic cells has both
diagnostic and pathogenetic importance. Although such homing is
incompletely understood, it generally involves cell adhesion and
migration mediated by a number of adhesion receptors and cytokines.
In this article, the potential importance of hyaluronan (HA) is
examined for the tissue homing of hairy cells (HCs) in hairy cell
leukemia (HCL). It is shown that HCs readily adhere to, and
spontaneously move on, HA-coated surfaces using CD44. This indicates
that activated CD44 and spontaneous movement on HA form part of the
intrinsically activated phenotype of HCs. Interleukin-8 (IL-8)
inhibited HC movement on HA, and this cell arrest was accompanied by
increased actin polymerization and a more pronounced association of
CD44 with the cytoskeleton. All of these findings are in sharp contrast to our previous observations with chronic lymphocytic leukemia cells,
which are nonmotile on HA, but in response to IL-8 become polarized and
motile using the receptor for HA-mediated motility rather than their
apparently inactive CD44. Immunohistochemical examination of HCL
tissues showed the ubiquitous presence of IL-8 and the prominence of HA
in bone marrow stroma and hepatic portal tracts. This suggests that
CD44-HA interactions are important in HC homing to these sites, but not
to splenic red pulp or hepatic sinusoids, where HA is largely
absent. Moreover, engagement of CD44 on HCs stimulates fibronectin
synthesis, an observation that is likely to be relevant
to the restriction of fibrosis in the disease to HC-infiltrated
areas containing HA.
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