| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
1 Molecular and Cellular Biology Research, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada; 2 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; 3 Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; 4 ImClone Systems, New York, New York and 5 R&D Systems Inc., Minneapolis, Minnesota
Requests for reprints: Robert S. Kerbel, Molecular and Cellular Biology Research, Sunnybrook and Women's College Health Sciences Centre, S-217, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5. Phone: 416-480-5711; Fax: 416-480-5884. E-mail: Robert.Kerbel{at}sw.ca
Angiogenesis and vasculogenesis are regulated in large part by several different growth factors and their associated receptor tyrosine kinases (RTKs). Foremost among these is the vascular endothelial growth factor (VEGF) family including VEGF receptor (VEGFR)-2 and -1. VEGFR ligand binding and biological activity are regulated at many levels, one of which is by a soluble, circulating form of VEGFR-1 (sVEGFR-1). This sVEGFR-1 can act as a competitive inhibitor of its ligand, serve as a possible biomarker, and play important roles in cancer and other diseases such as preeclampsia. Recombinant forms of sVEGFR-2 have been shown to have antiangiogenic activity, but a naturally occurring sVEGFR-2 has not been described previously. Here, we report such an entity. Having a molecular weight of 
160 kDa, sVEGFR-2 can be detected in mouse and human plasma with several different monoclonal and polyclonal anti-VEGFR-2 antibodies using both ELISA and immunoprecipitation techniques. In vitro studies have determined that the sVEGFR-2 fragment can be found in the conditioned media of mouse and human endothelial cells, thus suggesting that it may be secreted, similar to sVEGFR-1, or proteolytically cleaved from the cell. Potential biological activity of this protein was inferred from experiments in which mouse sVEGFR-2 could bind to VEGF-coated plates. Similar to sVEGFR-1 and other soluble circulating RTKs, sVEGFR-2 may have regulatory consequences with respect to VEGF-mediated angiogenesis as well as potential to serve as a quantitative biomarker of angiogenesis and antiangiogenic drug activity, particularly for drugs that target VEGF or VEGFR-2.
This article has been cited by other articles:
|
|
 |
|
  C Pieh, H Agostini, C Buschbeck, M Kruger, J Schulte-Monting, U Zirrgiebel, J Drevs, and W A Lagreze VEGF-A, VEGFR-1, VEGFR-2 and Tie2 levels in plasma of premature infants: relationship to retinopathy of prematurity Br. J. Ophthalmol., May 1, 2008; 92(5): 689 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M.L. Ebos, C. R. Lee, E. Bogdanovic, J. Alami, P. Van Slyke, G. Francia, P. Xu, A. J. Mutsaers, D. J. Dumont, and R. S. Kerbel Vascular Endothelial Growth Factor Mediated Decrease in Plasma Soluble Vascular Endothelial Growth Factor Receptor-2 Levels as a Surrogate Biomarker for Tumor Growth Cancer Res., January 15, 2008; 68(2): 521 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. L. Ebos, C. R. Lee, J. G. Christensen, A. J. Mutsaers, and R. S. Kerbel Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy PNAS, October 23, 2007; 104(43): 17069 - 17074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Brownbill, G. C. McKeeman, J. C. Brockelsby, I. P. Crocker, and C. P. Sibley Vasoactive and Permeability Effects of Vascular Endothelial Growth Factor-165 in the Term in Vitro Dually Perfused Human Placental Lobule Endocrinology, October 1, 2007; 148(10): 4734 - 4744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Norden-Zfoni, J. Desai, J. Manola, P. Beaudry, J. Force, R. Maki, J. Folkman, C. Bello, C. Baum, S. E. DePrimo, et al. Blood-Based Biomarkers of SU11248 Activity and Clinical Outcome in Patients with Metastatic Imatinib-Resistant Gastrointestinal Stromal Tumor Clin. Cancer Res., May 1, 2007; 13(9): 2643 - 2650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Petrovan, C. D. Kaplan, R. A. Reisfeld, and L. K. Curtiss DNA Vaccination Against VEGF Receptor 2 Reduces Atherosclerosis in LDL Receptor-Deficient Mice Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1095 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Srikiatkhachorn, C. Ajariyakhajorn, T. P. Endy, S. Kalayanarooj, D. H. Libraty, S. Green, F. A. Ennis, and A. L. Rothman Virus-Induced Decline in Soluble Vascular Endothelial Growth Receptor 2 Is Associated with Plasma Leakage in Dengue Hemorrhagic Fever J. Virol., February 15, 2007; 81(4): 1592 - 1600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Motzer, M. D. Michaelson, B. G. Redman, G. R. Hudes, G. Wilding, R. A. Figlin, M. S. Ginsberg, S. T. Kim, C. M. Baum, S. E. DePrimo, et al. Activity of SU11248, a Multitargeted Inhibitor of Vascular Endothelial Growth Factor Receptor and Platelet-Derived Growth Factor Receptor, in Patients With Metastatic Renal Cell Carcinoma J. Clin. Oncol., January 1, 2006; 24(1): 16 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Bocci, S. Man, S. K. Green, G. Francia, J. M. L. Ebos, J. M. du Manoir, A. Weinerman, U. Emmenegger, L. Ma, P. Thorpe, et al. Increased Plasma Vascular Endothelial Growth Factor (VEGF) as a Surrogate Marker for Optimal Therapeutic Dosing of VEGF Receptor-2 Monoclonal Antibodies Cancer Res., September 15, 2004; 64(18): 6616 - 6625. [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 |
