Differential regulation of hypoxia-induced CXCR4 triggering during B-cell development and lymphomagenesis.
Cancer Res
; 67(18): 8605-14, 2007 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-17875700
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, whereas 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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Linfoma de Células B
/
Receptores CXCR4
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Año:
2007
Tipo del documento:
Article
País de afiliación:
Italia