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Prepublished online as a Blood First Edition Paper on September 26, 2002; DOI 10.1182/blood-2002-02-0475.
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Blood, 15 February 2003, Vol. 101, No. 4, pp. 1487-1493
NEOPLASIA
Functional expression of the eotaxin receptor CCR3 in
CD30+ cutaneous T-cell lymphoma
Martin Kleinhans,
Adrian Tun-Kyi,
Michel Gilliet,
Marshall E. Kadin,
Reinhard Dummer,
Günter Burg, and
Frank O. Nestle
From the Department of Dermatology, University of
Zürich Medical School, Zürich, Switzerland;
Department of Dermatology, Medical School, J. W. Goethe-University, Frankfurt/Main, Germany; and the
Department of Pathology, Beth Israel Deaconess Medical Center and
Harvard Medical School, Boston, MA.
Little is known about mechanisms involved in skin-specific homing
of cutaneous T-cell lymphoma (CTCL). Chemokine/chemokine receptor
interactions have been implicated in the homing of lymphoma cells to
various tissue sites. We investigated tissue samples and tumor cell
suspensions of patients with CD30+ CTCL (n = 8) and
CD30 CTCL (mycosis fungoides, n = 6; Sézary
syndrome, n = 6) for expression of the chemokine receptors CCR3,
CCR4, and CCR8 and the CCR3 ligands eotaxin/CCL11, monocyte
chemoattractant protein 3 (MCP-3)/CCL7, and RANTES (regulated
on activation, normal T expressed and secreted)/CCL5. Of 8 CD30+ CTCLs, 7 expressed CCR3, 4 CCR4, and none CCR8. CCR3
expression was not found in skin tissue samples from 12 CD30 CTCLs. Coexpression of CCR3 and CD30 was
demonstrated by flow cytometry in tumor cell suspensions.
Internalization experiments demonstrated functionality of CCR3
expressed by freshly isolated tumor cells. Actin
polymerization as well as migration in response to eotaxin was
demonstrated in a CD30+ cutaneous lymphoma cell line. CCR3
ligand eotaxin/CCL11 was detected in lesional skin of CD30+
CTCL by immunohistochemistry, preferentially in tumor cells. Eotaxin/CCL11 expression in tumor cells was confirmed by
intracellular immunofluorescence. Analysis of cytokine expression
pattern of CCR3-bearing infiltrating cells showed a predominance of
interleukin-4 (IL-4) but not interferon- (IFN- )
protein expression,1 consistent with a T-helper 2 (Th-2) profile. These results suggest that expression of CCR3 and its ligand eotaxin/CCL11 plays a role in the recruitment and retention of CD30+ malignant T cells to the skin.

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