Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Kleinhans M,Tun-Kyi A,Gilliet M,Kadin ME,Dummer R,Burg G,Nestle FO

doi

10.1182/blood-2002-02-0475

subject

Has Abstract

pub_date

2003-02-15 00:00:00

pages

1487-93

issue

4

eissn

0006-4971

issn

1528-0020

pii

2002-02-0475

journal_volume

101

pub_type

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