Differential regulation of hypoxia-induced CXCR4 triggering during B-cell development and lymphomagenesis

Erich Piovan, Valeria Tosello, Stefano Indraccolo, Massimo Masiero, Luca Persano, Giovanni Esposito, Rita Zamarchi, Maurilio Ponzoni, Luigi Chieco-Bianchi, Riccardo Dalla-Favera, Alberto Amadori

Research output: Contribution to journalArticlepeer-review

Abstract

The chemokine receptor CXCR4 plays a central role in organ-specific homing and tumor spreading and is induced by hypoxia. B lymphocytes are exposed to low oxygen tensions during their development, but the influence of hypoxia on their physiology is poorly understood. Here, we show that hypoxia is associated with up-regulation of CXCR4 expression in human normal and malignant B cells, through both transcriptional and posttranslational mechanisms. However, a dichotomic functional response to CXCR4 triggering was observed: both peripheral B cells and lymphomas arising from mature B cells displayed increased responses to CXCR4 triggering under hypoxia, where as germinal center (GC) B cells as well as GC-derived lymphomas showed CXCR4 receptor desensitization. This phenomenon was associated with differential modulation of key signal-transducing molecules, including mitogen-activated protein kinase phosphatase-1 and regulator of G protein signaling molecule-1. The unresponsiveness of GC-derived lymphomatous B cells to CXCR4 triggering under hypoxia may have implications for the development and pathogenesis of GC-derived lymphoid tumors.

Original languageEnglish
Pages (from-to)8605-8614
Number of pages10
JournalCancer Research
Volume67
Issue number18
DOIs
Publication statusPublished - Sep 15 2007

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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