title: Up-regulation of the chemokine receptor CCR7 in classical but not in lymphocyte-predominant Hodgkin disease correlates with distinct dissemination of neoplastic cells in lymphoid organs.
abstract: Chemokines and chemokine receptors are key mediators for regulating cell traffic and positioning in both homeostatic and inflammatory conditions. It is also presumed that chemokines and their receptors are likely to play a critical role in the localization of malignant hematopoietic cells in their target organs. This study analyzed chemokine and chemokine receptor expression in several Hodgkin disease (HD)-derived cell lines and in HD tumors. All HD-derived cell lines expressed functional CCR7 and CXCR4 receptors. CCR7 up-regulation was mediated by constitutive NF-kappaB activity. Lymphoid tissues in HD revealed differential expression levels of CCR7, CXCR4, and CXCR5, depending on the distinct subtypes of HD. HD of the classical subtypes, predominantly located in the interfollicular zone, showed strong CCR7 and CXCR4 expression and moderate CXCR5 expression. In contrast, the nodular lymphocyte-predominant HD (NLP) subtype, regularly associated with follicular structures, exhibited no CCR7 reactivity but abundant CXCR4 staining. Their respective chemokine ligands showed marked expression by reactive cells within the tumors of classical HD and outside of the tumor nodules in NLPHD. Functionally, such differential chemokine receptor expression might contribute to specific localization and confinement of neoplastic cells within the target organs in the distinct HD entities.
authors.affiliation: Max Delbrück Center for Molecular Medicine and the Institute of Pathology, Klinikum Benjamin Franklin, Free University of Berlin, Germany.
authors.forename: Uta E
authors.initials: UE
authors.lastname: Höpken
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Foss
authors.forename: Dagmar
authors.initials: D
authors.lastname: Meyer
authors.forename: Michael
authors.initials: M
authors.lastname: Hinz
authors.forename: Korinna
authors.initials: K
authors.lastname: Leder
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Martin
authors.initials: M
authors.lastname: Lipp
mesh_terms: D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis; D006689:Hodgkin Disease / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: C515354:CCR4 protein, human; C515370:CCR7 protein, human; D018925:Chemokines; D016328:NF-kappa B; D012333:RNA, Messenger; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D019707:Receptors, Chemokine