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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1109-1116
CHEMOKINES
Up-regulation of the chemokine receptor CCR7 in classical but not
in lymphocyte-predominant Hodgkin disease correlates with distinct
dissemination of neoplastic cells in lymphoid organs
Uta E. Höpken,
Hans-Dieter Foss,
Dagmar Meyer,
Michael Hinz,
Korinna Leder,
Harald Stein, and
Martin Lipp
From the Max Delbrück Center for Molecular
Medicine and the Institute of Pathology, Klinikum Benjamin Franklin,
Free University of Berlin, Germany.
Chemokines and chemokine receptors are key mediators for regulating
cell traffic and positioning in both homeostatic and inflammatory conditions. It is also presumed that chemokines and their receptors are
likely to play a critical role in the localization of malignant hematopoietic cells in their target organs. This study analyzed chemokine and chemokine receptor expression in several Hodgkin disease
(HD)-derived cell lines and in HD tumors. All HD-derived cell lines
expressed functional CCR7 and CXCR4 receptors. CCR7 up-regulation was
mediated by constitutive NF- B activity. Lymphoid tissues in HD
revealed differential expression levels of CCR7, CXCR4, and CXCR5,
depending on the distinct subtypes of HD. HD of the classical
subtypes, predominantly located in the interfollicular zone, showed
strong CCR7 and CXCR4 expression and moderate CXCR5 expression. In
contrast, the nodular lymphocyte-predominant HD (NLP) subtype,
regularly associated with follicular structures, exhibited no CCR7
reactivity but abundant CXCR4 staining. Their respective chemokine
ligands showed marked expression by reactive cells within the tumors of
classical HD and outside of the tumor nodules in NLPHD. Functionally,
such differential chemokine receptor expression might contribute to
specific localization and confinement of neoplastic cells within the
target organs in the distinct HD entities.
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