title: Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV.
abstract: 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.
authors.affiliation: 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. narducci@idi.it
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Narducci
authors.forename: Enrico
authors.initials: E
authors.lastname: Scala
authors.forename: Antonella
authors.initials: A
authors.lastname: Bresin
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Caprini
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Picchio
authors.forename: Daniele
authors.initials: D
authors.lastname: Remotti
authors.forename: Gianluca
authors.initials: G
authors.lastname: Ragone
authors.forename: Francesca
authors.initials: F
authors.lastname: Nasorri
authors.forename: Marina
authors.initials: M
authors.lastname: Frontani
authors.forename: Diego
authors.initials: D
authors.lastname: Arcelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Giuseppe Alfonso
authors.initials: GA
authors.lastname: Lombardo
authors.forename: Giannandrea
authors.initials: G
authors.lastname: Baliva
authors.forename: Monica
authors.initials: M
authors.lastname: Napolitano
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Russo
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism / Q000494:pharmacology*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D009362:Neoplasm Metastasis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012751:Sezary Syndrome / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D006023:Glycoproteins; D019718:Receptors, CXCR4; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase