| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Vanderbilt University, Nashville, TN 37232
Impaired Ag-presenting function in dendritic cells (DCs) due to abnormal differentiation is an important mechanism of tumor escape from immune control. A major role for vascular endothelial growth factor (VEGF) and its receptors, VEGFR1/Flt-1 and VEGFR2/KDR/Flk-1, has been documented in hemopoietic development. To study the roles of each of these receptors in DC differentiation, we used an in vitro system of myeloid DC differentiation from murine embryonic stem cells. Exposure of wild-type, VEGFR1–/–, or VEGFR2–/– embryonic stem cells to exogenous VEGF or the VEGFR1-specific ligand, placental growth factor, revealed distinct roles of VEGF receptors. VEGFR1 is the primary mediator of the VEGF inhibition of DC maturation, whereas VEGFR2 tyrosine kinase signaling is essential for early hemopoietic differentiation, but only marginally affects final DC maturation. SU5416, a VEGF receptor tyrosine kinase inhibitor, only partially rescued the mature DC phenotype in the presence of VEGF, suggesting the involvement of both tyrosine kinase-dependent and independent inhibitory mechanisms. VEGFR1 signaling was sufficient for blocking NF-
B activation in bone marrow hemopoietic progenitor cells. VEGF and placental growth factor affect the early stages of myeloid/DC differentiation. The data suggest that therapeutic strategies attempting to reverse the immunosuppressive effects of VEGF in cancer patients might be more effective if they specifically targeted VEGFR1.
This article has been cited by other articles:
|
|
 |
|
  C. L. Roland, S. P. Dineen, K. D. Lynn, L. A. Sullivan, M. T. Dellinger, L. Sadegh, J. P. Sullivan, D. S. Shames, and R. A. Brekken Inhibition of vascular endothelial growth factor reduces angiogenesis and modulates immune cell infiltration of orthotopic breast cancer xenografts Mol. Cancer Ther., July 1, 2009; 8(7): 1761 - 1771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Loges, T. Schmidt, and P. Carmeliet "Antimyeloangiogenic" Therapy for Cancer by Inhibiting PlGF Clin. Cancer Res., June 1, 2009; 15(11): 3648 - 3653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Kurtagic, M. P. Jedrychowski, and M. A. Nugent Neutrophil elastase cleaves VEGF to generate a VEGF fragment with altered activity Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L534 - L546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Saint-Geniez, T. Kurihara, and P. A. D'Amore Role of Cell and Matrix-Bound VEGF Isoforms in Lens Development Invest. Ophthalmol. Vis. Sci., January 1, 2009; 50(1): 311 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ricciardi, A. R. Elia, P. Cappello, M. Puppo, C. Vanni, P. Fardin, A. Eva, D. Munroe, X. Wu, M. Giovarelli, et al. Transcriptome of Hypoxic Immature Dendritic Cells: Modulation of Chemokine/Receptor Expression Mol. Cancer Res., February 1, 2008; 6(2): 175 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Tian, S. Grimaldo, M. Fugita, J. Cutts, N. L. Vujanovic, and L.-Y. Li The Endothelial Cell-Produced Antiangiogenic Cytokine Vascular Endothelial Growth Inhibitor Induces Dendritic Cell Maturation J. Immunol., September 15, 2007; 179(6): 3742 - 3751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Huang, X. Chen, M. M. Dikov, S. V. Novitskiy, C. A. Mosse, L. Yang, and D. P. Carbone Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF Blood, July 15, 2007; 110(2): 624 - 631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Manning, J. G.M. Ullman, J. M. Leatherman, J. M. Asquith, T. R. Hansen, T. D. Armstrong, D. J. Hicklin, E. M. Jaffee, and L. A. Emens A Vascular Endothelial Growth Factor Receptor-2 Inhibitor Enhances Antitumor Immunity through an Immune-Based Mechanism Clin. Cancer Res., July 1, 2007; 13(13): 3951 - 3959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Li, A. S. Lalani, T. C. Harding, B. Luan, K. Koprivnikar, G. Huan Tu, R. Prell, M. J. VanRoey, A. D. Simmons, and K. Jooss Vascular Endothelial Growth Factor Blockade Reduces Intratumoral Regulatory T Cells and Enhances the Efficacy of a GM-CSF-Secreting Cancer Immunotherapy. Clin. Cancer Res., November 15, 2006; 12(22): 6808 - 6816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. F. Voelkel, R. W. Vandivier, and R. M. Tuder Vascular endothelial growth factor in the lung Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L209 - L221. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
