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Blood, 1 February 2005, Vol. 105, No. 3, pp. 931-939. Prepublished online as a Blood First Edition Paper on September 28, 2004; DOI 10.1182/blood-2004-03-0799. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0799v1 105/3/931    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Piovan, E. Articles by Amadori, A. Search for Related Content PubMed PubMed Citation Articles by Piovan, E. Articles by Amadori, A. Related Collections Immunobiology Neoplasia Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES Chemokine receptor expression in EBV-associated lymphoproliferation in hu/SCID mice: implications for CXCL12/CXCR4 axis in lymphoma generation Erich Piovan, Valeria Tosello, Stefano Indraccolo, Anna Cabrelle, Ilenia Baesso, Livio Trentin, Rita Zamarchi, Hirokazu Tamamura, Nobutaka Fujii, Gianpietro Semenzato, Luigi Chieco-Bianchi, and Alberto Amadori From the Department of Oncology and Surgical Sciences, Oncology Section, University of Padua, Italy; Istituto Nazionale per la Ricerca sul Cancro-IST, Genua, Italy; Department of Clinical and Experimental Medicine, Clinical Immunology Branch, University of Padua, Italy; Graduate School of Pharmaceutical Sciences, Kyoto University, Japan; Azienda Ospedaliera Padova, Padua, Italy; and Venetian Institute for Molecular Medicine, Padua, Italy. The mechanisms by which intraperitoneal injection of peripheral blood mono-nuclear cells (PBMCs) from Epstein-Barr virus (EBV)–seropositive donors into severe combined immunodeficient (SCID) mice gives rise to lymphomas (hu/SCID tumors) are far from clear. This study addressed whether chemokine receptors and their ligands could be implicated in this experimental model. CXCR4 was found to be highly expressed in hu/SCID tumors; surface expression of CXCR4 was prevalently limited to a tumor cell subset poorly expressing CD23, whereas the CXCR4 ligand, CXCL12, was predominantly expressed by the tumor subpopulation expressing CD23. In vitro inhibition of this autocrine/paracrine CXCL12/CXCR4 axis significantly inhibited lymphoma proliferation and survival. Furthermore, CXCL12 was expressed in cells recovered from the mouse peritoneal cavity early after PBMC transfer as well as by EBV-transformed B cells but not by resting or activated B lymphocytes; also, lymphoma development was associated with a dramatic increase in the levels of murine CXCL12 present in the peritoneal cavity. Finally, antagonizing the CXCL12/CXCR4 axis in vivo strongly counteracted lymphoma development. These studies demonstrate that CXCL12 expression may be associated with EBV infection and suggest that the CXCR4/CXCL12 axis may participate in the EBV-associated lymphomagenesis process in immunodeficient hosts. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Macor, C. Tripodo, S. Zorzet, E. Piovan, F. Bossi, R. Marzari, A. Amadori, and F. Tedesco In vivo Targeting of Human Neutralizing Antibodies against CD55 and CD59 to Lymphoma Cells Increases the Antitumor Activity of Rituximab Cancer Res., November 1, 2007; 67(21): 10556 - 10563. [Abstract] [Full Text] [PDF] E. Piovan, V. Tosello, S. Indraccolo, M. Masiero, L. Persano, G. Esposito, R. Zamarchi, M. Ponzoni, L. Chieco-Bianchi, R. Dalla-Favera, et al. Differential Regulation of Hypoxia-Induced CXCR4 Triggering during B-Cell Development and Lymphomagenesis Cancer Res., September 15, 2007; 67(18): 8605 - 8614. [Abstract] [Full Text] [PDF] P. Ame-Thomas, H. Maby-El Hajjami, C. Monvoisin, R. Jean, D. Monnier, S. Caulet-Maugendre, T. Guillaudeux, T. Lamy, T. Fest, and K. Tarte Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis Blood, January 15, 2007; 109(2): 693 - 702. [Abstract] [Full Text] [PDF] I. Airoldi, L. Raffaghello, E. Piovan, C. Cocco, B. Carlini, A. Amadori, M. V. Corrias, and V. Pistoia CXCL12 Does Not Attract CXCR4+ Human Metastatic Neuroblastoma Cells: Clinical Implications Clin. Cancer Res., January 1, 2006; 12(1): 77 - 82. [Abstract] [Full Text] [PDF]

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