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, Alberto Amadori

Research output: Contribution to journalArticle

Abstract

The mechanisms by which intraperitoneal injection of peripheral blood mononuclear 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.

Original languageEnglish
Pages (from-to)931-939
Number of pages9
JournalBlood
Volume105
Issue number3
DOIs
Publication statusPublished - Feb 1 2005

ASJC Scopus subject areas

  • Hematology

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