| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cell and Tumor Biology |
1 Department of Pediatrics, Divisions of Pediatric Hematology/Oncology and 2 Neuropathology; 3 Departments of Anatomy and Neurobiology and 4 Neurology, Washington University School of Medicine, St. Louis, Missouri; and 5 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
Requests for reprints: Joshua B. Rubin, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Washington University School of Medicine, Campus Box 8208, 660 South Euclid Avenue, St. Louis, MO 63110. Phone: 314-286-2790; Fax: 314-286-2892; E-mail: Rubin_J{at}kids.wustl.edu.
The chemokine receptor CXCR4 is expressed in many cancers where it may regulate tumor cell growth and migration. The role of CXCR4 in cancer will depend on it being in an activated, signaling state. To better define the significance of CXCR4 expression in cancer, we developed an antibody that can distinguish CXCR4 phosphorylated on serine 339, a residue previously identified as a site for ligand-induced phosphorylation. With this antibody, we investigated the mechanisms of CXCR4 phosphorylation and evaluated the phosphorylation status of CXCR4 in human astrocytomas. In vitro, phosphorylation of serine 339 occurred in response to CXCL12 or epidermal growth factor (EGF) treatment and was increased by protein kinase C activation. In all grades of astrocytomas, CXCR4 was expressed in tumor cells and some endothelial cells, whereas CXCL12 was present in endothelial cells and infiltrating microglia. We found that CXCR4 phosphorylated on serine 339 was present in tumor cells and vascular endothelial cells in all grades of astrocytoma. These data indicate that CXCR4 is expressed and activated in astrocytomas and that phosphorylation of CXCR4 can occur through ligand activation or transactivation via the EGF receptor. These studies extend the potential roles of CXCR4 in cancer to include functions associated with benign (grade 1) tumors. The ability to distinguish phosphorylated CXCR4 will be invaluable for the continued analysis of the role of CXCR4 in cancer and the development of CXCR4 antagonist therapy for patients suffering with primary tumors of the brain and other sites. (Cancer Res 2005; 65(24): 11392-9)
This article has been cited by other articles:
|
|
 |
|
  R. Grundler, L. Brault, C. Gasser, A. N. Bullock, T. Dechow, S. Woetzel, V. Pogacic, A. Villa, S. Ehret, G. Berridge, et al. Dissection of PIM serine/threonine kinases in FLT3-ITD-induced leukemogenesis reveals PIM1 as regulator of CXCL12-CXCR4-mediated homing and migration J. Exp. Med., August 31, 2009; 206(9): 1957 - 1970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hassan, C. Ferrario, U. Saragovi, L. Quenneville, L. Gaboury, A. Baccarelli, O. Salvucci, and M. Basik The Influence of Tumor-Host Interactions in the Stromal Cell-Derived Factor-1/CXCR4 Ligand/Receptor Axis in Determining Metastatic Risk in Breast Cancer Am. J. Pathol., July 1, 2009; 175(1): 66 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kwong, H. Kulbe, D. Wong, P. Chakravarty, and F. Balkwill An antagonist of the chemokine receptor CXCR4 induces mitotic catastrophe in ovarian cancer cells Mol. Cancer Ther., July 1, 2009; 8(7): 1893 - 1905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Zeng, Y. Xi Shi, I. J. Samudio, R.-Y. Wang, X. Ling, O. Frolova, M. Levis, J. B. Rubin, R. R. Negrin, E. H. Estey, et al. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML Blood, June 11, 2009; 113(24): 6215 - 6224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Mines, J. S. Goodwin, L. E. Limbird, F.-F. Cui, and G.-H. Fan Deubiquitination of CXCR4 by USP14 Is Critical for Both CXCL12-induced CXCR4 Degradation and Chemotaxis but Not ERK Activation J. Biol. Chem., February 27, 2009; 284(9): 5742 - 5752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Sengupta, S. Burbassi, S. Shimizu, S. Cappello, R. B. Vallee, J. B. Rubin, and O. Meucci Morphine Increases Brain Levels of Ferritin Heavy Chain Leading to Inhibition of CXCR4-Mediated Survival Signaling in Neurons J. Neurosci., February 25, 2009; 29(8): 2534 - 2544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Moll, M. B. Cossoy, E. Fisher, S. M. Staugaitis, B. H. Tucky, A. M. Rietsch, A. Chang, R. J. Fox, B. D. Trapp, and R. M. Ransohoff Imaging Correlates of Leukocyte Accumulation and CXCR4/CXCL12 in Multiple Sclerosis Arch Neurol, January 1, 2009; 66(1): 44 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Goldhoff, N. M. Warrington, D. D. Limbrick Jr., A. Hope, B. M. Woerner, E. Jackson, A. Perry, D. Piwnica-Worms, and J. B. Rubin Targeted Inhibition of Cyclic AMP Phosphodiesterase-4 Promotes Brain Tumor Regression Clin. Cancer Res., December 1, 2008; 14(23): 7717 - 7725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. McCandless, B. Zhang, M. S. Diamond, and R. S. Klein CXCR4 antagonism increases T cell trafficking in the central nervous system and improves survival from West Nile virus encephalitis PNAS, August 12, 2008; 105(32): 11270 - 11275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zagzag, M. Esencay, O. Mendez, H. Yee, I. Smirnova, Y. Huang, L. Chiriboga, E. Lukyanov, M. Liu, and E. W. Newcomb Hypoxia- and Vascular Endothelial Growth Factor-Induced Stromal Cell-Derived Factor-1{alpha}/CXCR4 Expression in Glioblastomas: One Plausible Explanation of Scherer's Structures Am. J. Pathol., August 1, 2008; 173(2): 545 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. McCandless, L. Piccio, B. M. Woerner, R. E. Schmidt, J. B. Rubin, A. H. Cross, and R. S. Klein Pathological Expression of CXCL12 at the Blood-Brain Barrier Correlates with Severity of Multiple Sclerosis Am. J. Pathol., March 1, 2008; 172(3): 799 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pattarozzi, M. Gatti, F. Barbieri, R. Wurth, C. Porcile, G. Lunardi, A. Ratto, R. Favoni, A. Bajetto, A. Ferrari, et al. 17 -Estradiol Promotes Breast Cancer Cell Proliferation-Inducing Stromal Cell-Derived Factor-1-Mediated Epidermal Growth Factor Receptor Transactivation: Reversal by Gefitinib Pretreatment Mol. Pharmacol., January 1, 2008; 73(1): 191 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Warrington, B. M. Woerner, G. C. Daginakatte, B. Dasgupta, A. Perry, D. H. Gutmann, and J. B. Rubin Spatiotemporal Differences in CXCL12 Expression and Cyclic AMP Underlie the Unique Pattern of Optic Glioma Growth in Neurofibromatosis Type 1 Cancer Res., September 15, 2007; 67(18): 8588 - 8595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Daginakatte and D. H. Gutmann Neurofibromatosis-1 (Nf1) heterozygous brain microglia elaborate paracrine factors that promote Nf1-deficient astrocyte and glioma growth Hum. Mol. Genet., May 1, 2007; 16(9): 1098 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Jones, G. J. Song, E. K. Greuber, and P. M. Hinkle Phosphorylation of the Endogenous Thyrotropin-releasing Hormone Receptor in Pituitary GH3 Cells and Pituitary Tissue Revealed by Phosphosite-specific Antibodies J. Biol. Chem., April 27, 2007; 282(17): 12893 - 12906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yang, E. Jackson, B. M. Woerner, A. Perry, D. Piwnica-Worms, and J. B. Rubin Blocking CXCR4-Mediated Cyclic AMP Suppression Inhibits Brain Tumor Growth In vivo Cancer Res., January 15, 2007; 67(2): 651 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Redjal, J. A. Chan, R. A. Segal, and A. L. Kung CXCR4 Inhibition Synergizes with Cytotoxic Chemotherapy in Gliomas. Clin. Cancer Res., November 15, 2006; 12(22): 6765 - 6771. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
