Involvement of CD44-hyaluronan interaction in malignant cell homing and fibronectin synthesis in hairy cell leukemia

Abstract

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.