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 language | English |
|---|---|
| Pages (from-to) | 8605-8614 |
| Number of pages | 10 |
| Journal | Cancer Research |
| Volume | 67 |
| Issue number | 18 |
| DOIs | |
| Publication status | Published - Sep 15 2007 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Differential regulation of hypoxia-induced CXCR4 triggering during B-cell development and lymphomagenesis. / Piovan, Erich; Tosello, Valeria; Indraccolo, Stefano; Masiero, Massimo; Persano, Luca; Esposito, Giovanni; Zamarchi, Rita; Ponzoni, Maurilio; Chieco-Bianchi, Luigi; Dalla-Favera, Riccardo; Amadori, Alberto.
In: Cancer Research, Vol. 67, No. 18, 15.09.2007, p. 8605-8614.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential regulation of hypoxia-induced CXCR4 triggering during B-cell development and lymphomagenesis
AU - Piovan, Erich
AU - Tosello, Valeria
AU - Indraccolo, Stefano
AU - Masiero, Massimo
AU - Persano, Luca
AU - Esposito, Giovanni
AU - Zamarchi, Rita
AU - Ponzoni, Maurilio
AU - Chieco-Bianchi, Luigi
AU - Dalla-Favera, Riccardo
AU - Amadori, Alberto
PY - 2007/9/15
Y1 - 2007/9/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-06-4722
DO - 10.1158/0008-5472.CAN-06-4722
M3 - Article
VL - 67
SP - 8605
EP - 8614
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 18
ER -