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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1108-1115.
Prepublished online as a Blood First Edition Paper on October 4, 2005; DOI 10.1182/blood-2005-04-1492.
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NEOPLASIA
Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV
Maria Grazia Narducci,
Enrico Scala,
Antonella Bresin,
Elisabetta Caprini,
Maria Cristina Picchio,
Daniele Remotti,
Gianluca Ragone,
Francesca Nasorri,
Marina Frontani,
Diego Arcelli,
Stefano Volinia,
Giuseppe Alfonso Lombardo,
Giannandrea Baliva,
Monica Napolitano, and
Giandomenico Russo
From the Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Laboratorio di Oncologia Molecolare, III e V Divisione Dermatologica, Laboratorio di Immunologia e Laboratorio di Patologia Vascolare, Via dei Monti di Creta, Rome, Italy; Azienda Ospedaliera San Camillo, Forlanini, Roma, Italy; and Dipartimento di Morfologia ed Embriologia, Università di Ferrara, Via Fossato di Mortara, Italy.
Sézary syndrome (SS) is a rare form of cutaneous T-cell lymphoma (CTCL) characterized by a distinct metastatic pattern mainly involving blood and skin. Chemokines and their receptors play a critical role in cellular recruitment and homing to tissues and in the metastatic process of several tumors including non-Hodgkin T-cell lymphomas (NHLs). Here we report that SS cells express a functionally active CXCR4 and that its ligand SDF-1 is abundantly produced in the skin, which represents the main destination of SS cell spreading. SDF-1 is normally inactivated by proteolytic cleavage by the CD26/dipeptidylpeptidase IV (DPPIV). The lack of CD26 from the cell surface is a hallmark of circulating SS cells. We also show that the CD26- phenotype is maintained also in skin-infiltrating neoplastic T lymphocytes and that SS-affected individuals exhibit a reduced activity of plasma soluble CD26. Finally, we observe that the addition of soluble CD26 reduces the migratory response of SS cells to SDF-1 whereas the inhibition of the CD26 peptidase activity in Hut78, a CD26+ CTCL cell line, enhances the SDF-1-induced migration of these cells. Our findings suggest that the SDF-1-CXCR4 axis could play an important role in skin homing of SS through the regulatory activity of CD26.

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