This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ebos, J. M.L. Articles by Kerbel, R. S. Search for Related Content PubMed PubMed Citation Articles by Ebos, J. M.L. Articles by Kerbel, R. S.

Vascular Endothelial Growth Factor–Mediated Decrease in Plasma Soluble Vascular Endothelial Growth Factor Receptor-2 Levels as a Surrogate Biomarker for Tumor Growth

¹ Sunnybrook Health Sciences Centre, Molecular and Cellular Biology Research and ² Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Requests for reprints: Robert S. Kerbel, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2M9. Phone: 416-480-5711; Fax: 416-480-5884. E-mail: Robert.Kerbel{at}sri.utoronto.ca.

Vascular endothelial growth factor (VEGF) is a potent proangiogenic protein that activates VEGF receptor (VEGFR) tyrosine kinases expressed by vascular endothelial cells. We previously showed that one of these receptors, VEGFR-2, has a truncated soluble form (sVEGFR-2) that can be detected in mouse and human plasma. Because activation of VEGFR-2 plays an important role in tumor angiogenesis, clinical interest in monitoring plasma sVEGFR-2 levels in cancer patients has focused on its potential exploitation as a surrogate biomarker for disease progression as well as assessing efficacy/activity of antiangiogenic drugs, particularly those that target VEGF or VEGFR-2. However, no preclinical studies have been done to study sVEGFR-2 during tumor growth or the mechanisms involved in its modulation. Using spontaneously growing tumors and both localized and metastatic human tumor xenografts, we evaluated the relationship between sVEGFR-2 and tumor burden as well as underlying factors governing protein level modulation in vivo. Our results show an inverse relationship between the levels of sVEGFR-2 and tumor size. Furthermore, using various methods of VEGF overexpression in vivo, including cell transfection and adenoviral delivery, we found plasma sVEGFR-2 decreases to be mediated largely by tumor-derived VEGF. Finally, in vitro studies indicate VEGF-mediated sVEGFR-2 modulation is the result of ligand-induced down-regulation of the VEGFR-2 from the cell surface. Taken together, these findings may be pertinent to further clinical exploitation of plasma sVEGFR-2 levels as a surrogate biomarker of VEGF-dependent tumor growth as well as an activity indicator of antiangiogenic drugs that target the VEGFR system. [Cancer Res 2008;68(2):521–9]

This article has been cited by other articles:

				Q. Guo, J. J. Carrero, X. Yu, P. Barany, A. R. Qureshi, M. Eriksson, B. Anderstam, M. Chmielewski, O. Heimburger, P. Stenvinkel, et al. Associations of VEGF and its receptors sVEGFR-1 and -2 with cardiovascular disease and survival in prevalent haemodialysis patients Nephrol. Dial. Transplant., June 26, 2009; (2009) gfp315v1. [Abstract] [Full Text] [PDF]

				C. G. Willett, D. G. Duda, E. di Tomaso, Y. Boucher, M. Ancukiewicz, D. V. Sahani, J. Lahdenranta, D. C. Chung, A. J. Fischman, G. Y. Lauwers, et al. Efficacy, Safety, and Biomarkers of Neoadjuvant Bevacizumab, Radiation Therapy, and Fluorouracil in Rectal Cancer: A Multidisciplinary Phase II Study J. Clin. Oncol., June 20, 2009; 27(18): 3020 - 3026. [Abstract] [Full Text] [PDF]

				J. Hasan, K. D. Beharry, A. M. Valencia, A. Strauss, and H. D. Modanlou Soluble Vascular Endothelial Growth Factor Receptor 1 in Tracheal Aspirate Fluid of Preterm Neonates at Birth May Be Predictive of Bronchopulmonary Dysplasia/Chronic Lung Disease Pediatrics, June 1, 2009; 123(6): 1541 - 1547. [Abstract] [Full Text] [PDF]

				C. Ruiz de Almodovar, D. Lambrechts, M. Mazzone, and P. Carmeliet Role and Therapeutic Potential of VEGF in the Nervous System Physiol Rev, April 1, 2009; 89(2): 607 - 648. [Abstract] [Full Text] [PDF]