title: CXCR3 and its binding chemokines in myeloma cells: expression of isoforms and potential relationships with myeloma cell proliferation and survival.
abstract: OBJECTIVE
  The chemokine receptor CXCR3, involved in chemotaxis, is expressed on normal and malignant B cells and plasma cells. Recent data suggest that CXCR3-binding chemokines may also regulate proliferation and survival in endothelial cells through the interaction with two distinct isoforms of CXCR3 (CXCR3-A and CXCR3-B).
  
  
  METHODS
  We evaluated the potential expression of CXCR3 isoforms in myeloma cells, also investigating whether CXCR3 expression is affected by cell cycle and apoptosis. Furthermore, we assessed the effect of CXCR3 activation on myeloma cell proliferation and survival.
  
  
  RESULTS
  We found that CXCR3 is widely expressed on human myeloma cell lines and freshly purified myeloma cells. The presence of both CXCR3 isoforms, CXCR3-A and CXCR3-B, was observed in myeloma cells with different ratios of expression. Interestingly, we found that CXCR3 expression in myeloma cell was cell cycle dependent and that myeloma growth factors inhibited CXCR3 expression in myeloma cells. On the other hand, we found that FAS (CD95)-mediated apoptosis up-regulated CXCR3 expression. A similar behavior was observed for the CXCR3-binding chemokines. Finally we found that the activation of CXCR3 on myeloma cells by CXCL10/IP-10 partially blunted FAS-mediated apoptosis in myeloma cells that express CXCR3-A and that high concentrations of CXCL10/IP-10 inhibit myeloma cell proliferation. INTERPRETATION AND CONCLUSIONS Our data indicate that myeloma cells express the CXCR3 system with patterns correlated to cell cycle and apoptosis and that CXCR3 activation may affect myeloma cell survival and proliferation.
authors.affiliation: Hematology and CTMO, University of Parma, Italy. N_giuliani@yahoo.com
authors.forename: Nicola
authors.initials: N
authors.lastname: Giuliani
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bonomini
authors.forename: Paola
authors.initials: P
authors.lastname: Romagnani
authors.forename: Mirca
authors.initials: M
authors.lastname: Lazzaretti
authors.forename: Francesca
authors.initials: F
authors.lastname: Morandi
authors.forename: Simona
authors.initials: S
authors.lastname: Colla
authors.forename: Sara
authors.initials: S
authors.lastname: Tagliaferri
authors.forename: Laura
authors.initials: L
authors.lastname: Lasagni
authors.forename: Francesco
authors.initials: F
authors.lastname: Annunziato
authors.forename: Monica
authors.initials: M
authors.lastname: Crugnola
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rizzoli
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C515187:CXCR3 protein, human; D018925:Chemokines; D020033:Protein Isoforms; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine