title: CXCR4 expression enhances diffuse large B cell lymphoma dissemination and decreases patient survival.
abstract: The chemokine receptor CXCR4 has been implicated in the migration and trafficking of malignant B cells in several haematological malignancies. Over-expression of CXCR4 has been identified in haematological tumours, but data concerning the role of this receptor in diffuse large B cell lymphoma (DLBCL) are lacking. CXCR4 is a marker of poor prognosis in various neoplasms, correlating with metastatic disease and decreased survival of patients. We studied CXCR4 involvement in cell migration in vitro and dissemination in vivo. We also evaluated the prognostic significance of CXCR4 in 94 biopsies of DLBCL patients. We observed that the level of expression of CXCR4 in DLBCL cell lines correlated positively with in vitro migration. Expression of the receptor was also associated with increased engraftment and dissemination, and decreased survival time in NOD/SCID mice. Furthermore, administration of a specific CXCR4 antagonist, AMD3100, decreased dissemination of DLBCL cells in a xenograft mouse model. In addition, we found that CXCR4 expression is an independent prognostic factor for shorter overall survival and progression-free survival in DLBCL patients. These results show that CXCR4 mediates dissemination of DLBCL cells and define for the first time its value as an independent prognostic marker in DLBCL patients.
authors.affiliation: Grup d'Oncogènesi i Antitumorals, lnstitut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain; Department of Biochemistry and Molecular Biology, Universitat de Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomecidicina (CIBER-BBN), Barcelona, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Moreno
authors.forename: Rosa
authors.initials: R
authors.lastname: Bosch
authors.forename: Rebeca
authors.initials: R
authors.lastname: Dieguez-Gonzalez
authors.forename: Silvana
authors.initials: S
authors.lastname: Novelli
authors.forename: Ana
authors.initials: A
authors.lastname: Mozos
authors.forename: Alberto
authors.initials: A
authors.lastname: Gallardo
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Pavón
authors.forename: María Virtudes
authors.initials: MV
authors.lastname: Céspedes
authors.forename: Albert
authors.initials: A
authors.lastname: Grañena
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcoceba
authors.forename: Oscar
authors.initials: O
authors.lastname: Blanco
authors.forename: Marcos
authors.initials: M
authors.lastname: Gonzalez-Díaz
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
authors.forename: Ramon
authors.initials: R
authors.lastname: Mangues
authors.forename: Isolda
authors.initials: I
authors.lastname: Casanova
mesh_terms: D000818:Animals; D001596:Benzylamines; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D000080027:Cyclams; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016403:Lymphoma, Large B-Cell, Diffuse / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
chemical_list: D001596:Benzylamines; C527276:CXCR4 protein, human; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: CXCR4; cell dissemination; cell migration; diffuse large B cell lymphoma; prognostic marker