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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-gamma (IFN-gamma ) 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.

© 2003 by The American Society of Hematology.
 

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